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Background Spastic Paraplegia type 7 (SPG7) is one of the most common autosomal recessive Hereditary Spastic Paraplegias (HSP); Spastic Paraplegias (SPGs) can present as hereditary ataxias. However, ataxia is frequently the symptom of presentation of many other hereditary/sporadic disorders, such as Multiple system atrophy type C (MSA-C), an α-synuclein sporadic neurodegenerative disorder, in which cerebellar ataxia is one of the main clinical features. Dopamine Transporter imaging (DAT-SCAN), associated with clinical features, can be a helpful tool in order to distinguish MSA-C from other causes of ataxia. Case-presentation We present the case of a 70-year-old man with gait difficulties over a period of 3 years and frequent backward/lateral falls. He also reported urinary urge incontinence, but no symptoms that are compatible with orthostatic hypotension. On neurological examination he showed ataxic gait, spasticity in the left lower limb and trunk and limb ataxia, especially on the left side. Mild hypokinesia was found in all 4 limbs, especially in the left foot. MRI revealed atrophy of the cerebellar hemispheres and vermis. DAT-SCAN imaging revealed bilateral nigro-striatal degeneration, which was compatible with a diagnosis of possible MSA-C. Considering the atypical disease course (the patient walked without any support after 3 years), we carried out a genetic investigation for Ataxia, and a mutation in SPG7 was found. Conclusions DAT-SCAN imaging, evaluated together with the clinical findings, can be useful for differentiating MSA from other possible causes of adult-onset Ataxia. Indeed, patients with MSA-C generally show a decreased uptake of dopamine transporters in DAT-SCAN imaging. Ours is the first case reported in the literature of a patient with SPG7 mutation with nigrostriatal degeneration and a clinical presentation of a possible MSA-C. Performing genetic investigations in patients with an atypical disease course is important to avoid MSA-mimicries. Identifying the correct diagnosis is important not only for prognostic reasons, but also for possible future genetic therapies.

Aphasia induced by an infratentorial stroke has rarely been reported, and its mechanism has not been fully identified. We evaluated two individuals who had been admitted to Saiseikai Kumamoto Hospital in Kumamoto, Japan, due to acute ischemic stroke in order to determine whether their aphasia was induced by an infratentorial stroke. The first patient, a 59-year-old man with a history of left parietal embolic stroke with very mild sequelae of anomia, developed Wernicke's aphasia, nonfluent speech, and right limb ataxia as a result of the stroke. The second patient, a 76-year-old woman with a history of chronic renal failure, experienced transcortical sensory aphasia and right one-and-a-half syndrome as a result of the stroke. Both patients' recent ischemic lesions were limited to the right cerebellar hemisphere and the right medial portion of the midbrain. However, SPECT showed low-uptake lesions in both patients' left cerebral hemisphere that did not include the recent ischemic lesions but that had spread to an extent that was difficult to be explained by the old or recent ischemic lesions and that might be responsible for their recent aphasia. We believe that the aphasia experienced by these two patients may have been caused by crossed cerebello-cerebral diaschisis.

INTRODUÇÃO: As ataxias cerebelares são um extenso grupo de doenças, que causam diversos distúrbios na marcha e no equilíbrio que comprometem seriamente a qualidade de vida, sem opções de tratamento eficazes. A cinesioterapia é a base de programas multifacetados que incorporam mais de um enfoque, como o treinamento de coordenação e equilíbrio. Recentemente, a estimulação transcraniana por corrente contínua (tDCS) sobre o cerebelo surgiu como uma intervenção para melhorar os distúrbios do equilíbrio. OBJETIVO: Descrever a aplicação simultânea de tDCS anódica cerebelar e cinesioterapia, em sessões múltiplas diárias para reabilitação da ataxia cerebelar. MATERIAIS E MÉTODOS: Este relato de caso incluiu um paciente do sexo masculino, de 34 anos, com história de ataxia espinocerebelar há 10 anos. Seus principais objetivos eram melhorar a marcha e o equilíbrio. Ele apresentava ataxia axial e apendicular, dificuldades na marcha e no equilíbrio. O protocolo de estimulação do cerebelo consistiu na aplicação de tDCS por 20 minutos, 2mA, diariamente, durante duas semanas, com ânodo posicionado sobre o ínion e cátodo sobre o músculo deltóide direito. A cinesioterapia simultânea incluiu exercícios funcionais progressivos com objetivo principal de treinamento de equilíbrio. RESULTADOS: A melhora clínica foi particularmente evidenciada por uma redução de 4 pontos na Escala para Avaliação e Graduação da Ataxia após 10 sessões, enquanto a literatura recomenda a eficácia de uma nova terapia que retardaria a progressão da ataxia em 1 ponto por ano. CONCLUSÃO: Nossos resultados sugerem que a associação entre tDCS e cinesioterapia foi eficaz neste paciente; as sessões de tDCS foram seguras e bem toleradas e podem ter desempenhado um papel na melhora nos testes funcionais. Novos estudos controlados envolvendo um número maior de pacientes são necessários para analisar os benefícios destas técnicas combinadas para maximizar a reabilitação motora nesta população.

After extensive evaluation, one-third of patients affected by polyneuropathy remain undiagnosed and are labelled as having chronic idiopathic axonal polyneuropathy, which refers to a sensory or sensory-motor, axonal, slowly progressive neuropathy of unknown origin. Since a sensory neuropathy/neuronopathy is identified in all patients with genetically confirmed RFC1 cerebellar ataxia, neuropathy, vestibular areflexia syndrome, we speculated that RFC1 expansions could underlie a fraction of idiopathic sensory neuropathies also diagnosed as chronic idiopathic axonal polyneuropathy. We retrospectively identified 225 patients diagnosed with chronic idiopathic axonal polyneuropathy (125 sensory neuropathy, 100 sensory-motor neuropathy) from our general neuropathy clinics in Italy and the UK. All patients underwent full neurological evaluation and a blood sample was collected for RFC1 testing. Biallelic RFC1 expansions were identified in 43 patients (34%) with sensory neuropathy and in none with sensory-motor neuropathy. Forty-two per cent of RFC1-positive patients had isolated sensory neuropathy or sensory neuropathy with chronic cough, while vestibular and/or cerebellar involvement, often subclinical, were identified at examination in 58%. Although the sensory ganglia are the primary pathological target of the disease, the sensory impairment was typically worse distally and symmetric, while gait and limb ataxia were absent in two-thirds of the cases. Sensory amplitudes were either globally absent (26%) or reduced in a length-dependent (30%) or non-length dependent pattern (44%). A quarter of RFC1-positive patients had previously received an alternative diagnosis, including Sjögren’s syndrome, sensory chronic inflammatory demyelinating polyneuropathy and paraneoplastic neuropathy, while three cases had been treated with immune therapies., Currò et al. investigate the prevalence of RFC1 expansions in a cohort of patients with chronic idiopathic axonal polyneuropathy. RFC1 expansions were found in 34% of patients with sensory neuropathy, but in none with sensory-motor neuropathy. Clinical features and diagnostic clues that should lead to suspicion of RFC1 neuropathy are discussed.

Isolated pontine infarction accounts for 7% of all ischemic strokes. Millard-Gubler syndrome is a clinical syndrome which occurs following lesions involving the ventral portion of the caudal pons, resulting in classic clinical features such as ipsilateral abducens and facial nerve palsy and contralateral hemiparesis. We report the case of a 55-year-old male patient having presented to the Yehuleshet Specialty Clinic 6 years back with sudden-onset dysarthria and appendicular ataxia of 10 days duration. He reported having right hemibody weakness and blurred vision, which have significantly improved since then. He had a history of smoking of 30 pack-years. However, he quit smoking 8 years ago. There was no history of prior stroke, transient ischemic attack, diabetes, hypertension, head trauma, or dyslipidemia. On examination, he had horizontal left gaze palsy with horizontal nystagmus suggesting left-sided 6th cranial nerve palsy. He had mild left-sided facial palsy causing dysarthric speech. Right upper limb dysmetria was observed during examination; otherwise, motor, sensory, fundus, and gait examination results were normal. He had low serum vitamin D. Brain magnetic resonance imaging examination showed a 25 × 10 mm segmental lesion in the left median pons involving the basis pontis and tegmentum section. The lesion had T2 and T1 abnormal prolongation with no diffusion restriction, suggesting a subacute pontine infarct. The patient was managed with aspirin 325 mg, atorvastatin 80 mg, physical therapy, and vitamin D supplementation, and advised on behavioral risk factors. Six years after his isolated pontine infarction, the patient is fully recovered from dysarthria, facial palsy, hemiparesis, right-sided appendicular ataxia, and horizontal nystagmus, and the follow-up brain MRI showed radiological evidence of chronic paramedian pontine perforator infarction. Millard-Gubler syndrome may present with cerebellar ataxia if the paramedian pontine infarction area slightly extends laterally, affecting the middle cerebellar peduncles. Isolated pontine infarction may have a good prognosis if diagnosed and managed early.

Rhombencephalitis is an orphan disease of multiple causes that may manifest with facial palsy, limb ataxia and reduced consciousness. Up to now it is described after COVID-19 infection and in this (personal) case was found up to 8 weeks after Comirnaty vaccination. So far, we do not fully understand the pathophysiological characteristics of encephalitis associated with SARS-CoV-2. In rare cases, vaccination may cause an immunological reaction and delayed inflammation, the consequences of which we have not yet deciphered. Rhombencephalitis should be considered as a rare potential mRNA-associated vaccination side effect. Supplementary Information The online version contains supplementary material available at 10.1186/s42466-021-00156-7.

A 45-year-old man with a history of testicular seminoma treated 8 years earlier presented with chronic progressive truncal and limb ataxia, progressive sensorineural hearing loss, and episodic vertigo. Eye movement and neuro-otology examinations showed localizing abnormalities to the bilateral cerebellar flocculus, vermis, and bilateral cerebellar hemispheres. Audiometric testing showed bilateral symmetric sensorineural hearing loss. There was a normal MRI of the brain. Cerebrospinal fluid (CSF) showed modest lymphocytic pleocytosis, and there was an elevated serum choriogonadotrophic hormone. An abdominal CT scan showed a solitary, large retroperitoneal lymph node, and histopathologic examination of the node biopsy showed granulomatous inflammation without microorganisms; eventually, immunohistochemical markers confirmed the diagnosis of metastatic seminoma. Although normal neuroimaging and inflammatory CSF reaction suggested a paraneoplastic etiology, the initial paraneoplastic antibody testing was negative. Subsequent investigation identified a positive kelch-11 protein antibody, thus confirming the paraneoplastic connection between the metastatic seminoma and the subacute neurologic-cochleovestibular syndrome.

The objective of this study is to report the clinical characteristics and treatment of patients with progressive cerebellar ataxia associated with anti-GAD antibodies. We performed a retrospective review of all patients with anti-GAD ataxia managed at the Sheffield Ataxia Centre over the last 25 years. We identified 50 patients (62% females) with anti-GAD ataxia. The prevalence was 2.5% amongst 2000 patients with progressive ataxia of various causes. Mean age at onset was 55 and mean duration 8 years. Gaze-evoked nystagmus was present in 26%, cerebellar dysarthria in 26%, limb ataxia in 44% and gait ataxia in 100%. Nine patients (18%) had severe, 12 (24%) moderate and 29 (58%) mild ataxia. Ninety percent of patients had a history of additional autoimmune diseases. Family history of autoimmune diseases was seen in 52%. Baseline MR spectroscopy of the vermis was abnormal at presentation in 72%. Thirty-five patients (70%) had serological evidence of gluten sensitivity. All 35 went on gluten-free diet (GFD). Eighteen (51%) improved, 13 (37%) stabilised, 3 have started the GFD too recently to draw conclusions and one deteriorated. Mycophenolate was used in 16 patients, 7 (44%) improved, 2 stabilised, 6 have started the medication too recently to draw conclusions and one did not tolerate the drug. There is considerable overlap between anti-GAD ataxia and gluten ataxia. For those patients with both, strict GFD alone can be an effective treatment. Patients with anti-GAD ataxia and no gluten sensitivity respond well to immunosuppression.

Introduction Due to diverse symptoms of spinocerebellar ataxia type 3 (SCA3) and the high prevalence of SCA3 in China, a more in-depth study of Chinese SCA3 patients in a large cohort is well merited. Methods During the last 10 years, 730 patients and 133 premanifest individuals from 667 SCA3 families genetically confirmed to have SCA3 were enrolled from three leading academic hospitals in China. The clinical profile and genotype-phenotype correlation were analyzed. Results A quadratic equation best explained the relationship between the logarithmically transformed age at onset (AAO) and expanded CAG repeats (expCAGs) (r2 = 0.634, p 10 years. Intriguingly, onset after parturition happened in 10 female patients with the AAO of 26.7 ± 4.3 years and the expCAG of 77.4 ± 1.4 repeats. Five out of 12 patients with subtype V and larger expCAGs (78.8 ± 4.8 repeats) suffered from spastic gait initially, and 10 out of 12 showed no limb ataxia. Nystagmus happened most frequently (10.5%) in premanifest individuals. Conclusion We demonstrated the genotype-phenotype correlation in the largest cohort of SCA3 individuals to date, and interestingly found some new phenomena in Chinese SCA3 individuals.

Guillain-Barré (GBS) and Fisher (FS) syndromes rarely recur and the characteristics of recurrence have not been fully elucidated. We describe the cases of 2 patients with GBS or FS that recurred more than twice and who were subsequently diagnosed with aplastic anemia. Case 1 was a 66-year-old man who was diagnosed with aplastic anemia 10 months before admission with limb ataxia and a sensory disturbance of the distal limbs that developed 3 days after an upper respiratory tract infection. He had a history of double vision with ataxia at the ages of 38 and 56 years. Case 2 was a 66-year-old woman who had been treated for aplastic anemia 1 year previously. She had a history of upper limb weakness after upper respiratory tract infections at the ages of 39 and 60 years. Tendon reflexes were absent in both patients at the time of onset and they were respectively diagnosed with FS and GBS and treated with intravenous immunoglobulin. No neurological deficits persisted. Blood findings showed that both were positive for IgG type ganglioside antibodies and HLA-DR15. The positive HLA-DR15 might have been associated with the recurrent GBS or FS and the development of aplastic anemia.

The patient was a 64-year-old man presented with difficulty in walking, articulation, and swallowing, as well as cognitive impairment. He had refractory microcytic anemia and diabetes mellitus. His serum levels of iron, copper, and ceruloplasmin were low. Magnetic resonance imaging suggested iron deposition in the basal ganglia, thalami, cerebellar dentate nuclei, and cerebral and cerebellar cortices. He was diagnosed with aceruloplasminemia after a ceruloplasmin gene analysis. Iron chelation therapy with deferasirox improved his anemia and cerebellar symptoms, which included dysarthria and limb ataxia. The present study and previous reports indicate that cerebellar symptoms with aceruloplasminemia might respond to deferasirox in less than one year.

ObjectiveTo investigate the efficacy of rovatirelin, a thyrotropin-releasing hormone analogue, for ataxias in patients with spinocerebellar degeneration (SCD).MethodsTwo multicentre, randomised, double-blind, placebo-controlled phase 3 studies (KPS1301, KPS1305) enrolled patients with predominant cerebellar ataxia, including SCA6, SCA31 or cortical cerebellar atrophy. KPS1301 enrolled patients with truncal ataxia and KPS1305 enrolled patients with truncal and limb ataxia. Each study included 4 weeks of pretreatment, a 28-week or 24-week treatment period and 4 weeks of follow-up. Patients were randomised (1:1:1) to rovatirelin (1.6 or 2.4 mg) or placebo in KPS1301, and randomised (1:1) to rovatirelin 2.4 mg or placebo in KPS1305. The primary endpoint was change in Scale for the Assessment and Rating of Ataxia (SARA) total scores. Pooled analysis was performed in patients who met the SARA recruitment criteria of KPS1305.ResultsFrom October 2013 to May 2014, KPS1301 enrolled 411 patients; 374 were randomised to rovatirelin 1.6 mg (n=125), rovatirelin 2.4 mg (n=126) or placebo (n=123). From November 2016 to August 2017, KPS1305 enrolled 241 patients; 203 were randomised to rovatirelin 2.4 mg (n=101) or placebo (n=102). The primary endpoint showed no significant difference between rovatirelin and placebo in these two studies. In the pooled analysis (n=278), the difference between rovatirelin 2.4 mg (n=140) and placebo (n=138) was –0.61 (–1.64 vs –1.03; 95% CI –1.16 to –0.06; p=0.029) in the adjusted mean change in the SARA total score.ConclusionsRovatirelin is a potentially effective treatment option for SCD.Trial registration numberNCT01970098; NCT02889302

Progressive supranuclear palsy (PSP) is characterized by supranuclear gaze palsy, dystonic rigidity of the neck and upper trunk, frequent falls and mild cognitive impairment. Cerebellar ataxia is one of the exclusion criteria given by the National Institute of Neurological Disorders and Stroke and the Society for Progressive Supranuclear Palsy. As a result, pathologically proven PSP patients exhibiting cerebellar ataxia have often been misdiagnosed with spinocerebellar degeneration, specifically multiple system atrophy with predominant cerebellar ataxia (MSA-C). However, more recently, it has been recognized that patients with PSP can present with truncal and limb ataxia as their initial symptom and/or main manifestation. These patients can be classified as having PSP with predominant cerebellar ataxia (PSP-C), a new subtype of PSP. Since the development of this classification, patients with PSP-C have been identified primarily in Asian countries, and it has been noted that this condition is very rare in Western communities. Furthermore, the clinical features of PSP-C have been identified, enabling it to be distinguished from other subtypes of PSP and MSA-C. In this review, we describe the clinical and neuropathological features of PSP-C. The hypothesized pathophysiology of cerebellar ataxia in PSP-C is also discussed.

Background Guillain-Barre syndrome (GBS) is the broad term used to describe a number of related acute autoimmune neuropathies, which together form a continuous spectrum of variable and overlapping syndromes. Bifacial weakness with paresthesias (BFP) is a rare variant of GBS, characterized by isolated facial diplegia in the absence of ophthalmoplegia, ataxia, or limb weakness, and it is usually associated with distal limb paresthesias. Case description An 8-year-old boy was brought to our attention; because 5 days before coming to the hospital, he noticed he could no longer smile. Bilateral facial droop and inability to close both eyes were evident along with slight paresthesias at the hands and feet and gait disturbances. He progressively developed hypophonia, dysarthria, dysphagia associated with dysmetria, and limb ataxia. Nerve conduction studies showed a demyelinating polyneuropathy. Brain and spine magnetic resonance imaging (MRI) revealed contrast enhancement of both facial nerves and cauda equina nerve roots along with a hyperintense signal of the periaqueductal gray matter, superior cerebellar peduncles, and pontine tegmentum. Because BFP is not typically associated with other cranial neuropathies or ataxia, these clinical features along with peculiar MRI findings supported the diagnosis of "BFP plus." Finally, it can be speculated that this case configures a rare overlap between BFP and the other GBS variants, such as Bickerstaff encephalitis. Conclusions This atypical case underlines the potential role of MRI in contributing to refining the nosological classification of GBS spectrum and optimizing individual treatment, especially in children where unusual manifestations are not infrequent and neurological examination is more challenging.

Introduction Amyotrophy in Creutzfeldt-Jakob Disease (CJD) is rarely a conspicuous clinical finding. The overlap of CJD (a prionopathy) and motor neuron disease is reported in the literature but it remains to be established whether the neuronopathy is an integral part of CJD presentation, or, whether this represents a distinct variety. Our case describes a male patient with clincopathological diagnosis of sporadic CJD along with evidence of motor neuronopathy on nerve conduction studies. Case Summary At presentation to our neurology service, the patient was a 72-year-old male, living at home with his wife. He was initially referred for progressive short-term memory loss, personality change, and gait disturbance. On review, it was noted that in addition to gait and limb ataxia, and cognitive impairment, he demonstrated prominent generalised fasciculation. Nerve conduction and electromyography studies showed normal nerve conduction but fasciculations in proximal and distal muscle groups of the left upper and lower limbs, in keeping with a motor neuronopathy. CSF 14-3-3 and EEG provided little bearing. MRI demonstrated progressive T2-hyperintense, diffusion-restricted lesions in the bilateral basal ganglia, thalami and medial frontal cortices consistent with CJD. Post-mortem examination demonstrated spongiform encephalopathy and immunohistological staining (12F10) in-keeping with diagnosis of CJD. Conclusion In our patient, the combination of clinical and neurophysiologic features of motor neuron disease and a confirmed diagnosis of Creutzfeldt-Jakob Disease raises the vexed question of whether this represents a distinct overlap syndrome or an infrequent manifestation of the same pathology. Further research is required to establish this.

Autoimmune and paraneoplastic movement disorders are increasingly recognized as a result of improved methods in detecting antibodies directed against intracellular, membrane, and other antigens.1 High concentrations of anti-glutamic acid decarboxylase 65 (GAD65) antibodies are associated with several neurologic syndromes including stiff-person syndrome, epilepsy, limbic encephalitis, and cerebellar ataxia.2 Anti-GAD65-associated cerebellar ataxia is typically generalized with prominent gait disturbance and eye movement abnormalities.1 Limb ataxia is present in 60-70% of patients.3 Here we present 2 unusual cases of hemiataxia associated with high concentrations of anti-GAD65 antibodies.

Friedreich's ataxia is a rare degenerative neuromuscular disorder, caused by a homozygous GAA triplet repeat expansion in the frataxin (FXN) gene, with a broad clinical phenotype characterized by progressive gait and limb ataxia, dysarthria, and loss of lower limb reflexes; cardiac involvement is represented by hypertrophic cardiomyopathy, ventricular arrhythmias, and sudden cardiac deaths. Currently, no definite therapy is available, while many drugs are under investigation; for this reasons, we need markers of short‐ and long‐term treatment efficacy acting on different tissue for trial evaluation. We describe the case of a 21‐year‐old patient affected by Friedreich's ataxia on wheel‐chair, with initial cardiac involvement and electrocardiographic features characterized by thiamine treatment‐related negative T wave and QTc variations. We discuss plausible physiopathology and potential ECG role implications as an intermediate marker of treatment response in future clinical trials considering patients affected by Friedreich's ataxia.

Infarcts involving the thalamus can yield many deficits, including sensory syndromes, altered consciousness, and cognitive disturbances, depending on the thalamic vascular territory involved. Isolated truncal contrapulsion due to pure thalamic infarct has been rarely reported. Truncal lateropulsion is a compelling sensation of being pulled toward one side that cannot be explained by weakness or limb ataxia. It is commonly reported in lateral medullary infarcts. It may occur with lesions that involve the peripheral vestibular system, brainstem, cerebellum, basal ganglia, ponto-mesencephalic, and thalamic lesions. We hereby report a 64-year-old woman who presented with truncal contrapulsion as the sole manifestation of an acute right lateral thalamic infarct.

A previously independent 64-year-old man presented to his local hospital with new-onset diplopia and dysarthria while watching television. Over the following days, he developed painless perioral and upper limb sensory disturbance, gait unsteadiness and limb ataxia, most pronounced in the upper limbs. He was initially admitted and treated for a cerebrovascular event, followed by a period of failed rehabilitation. At 6-week review, his symptoms had worsened, and he required the assistance of two people to walk short distances. He was then transferred to a regional neurology unit. It was uncertain whether his symptoms had stabilised or progressed over the preceding fortnight. He had no other neurological symptoms, normal bladder and bowel function, and no history of preceding illness. Table 1 provides the background history. View this table: Table 1 Patient’s clinical and social background Assessment of eye movements identified a complex ophthalmoplegia, with complete failure of right eye abduction. Upgaze was bilaterally limited to 45° and adduction was partially restricted. There was no nystagmus. He described perioral numbness and was unaware of food boluses within his mouth, though objective testing was normal. Tongue movements were slowed but symmetrical. There was no fasciculation and his swallow appeared normal. His speech was dysarthric but intelligible and had a subtle nasal character. There were no other cranial nerve signs. Neck flexion and extension were normal. Tone was normal in all four limbs. His strength was symmetrically reduced in the upper limbs with the Medical Research Council (MRC) grade 4 proximally and 4− in the small finger muscles. Lower limb strength was MRC grade 4+ at hip flexion and 5 in all other muscle groups. He could not stand due to unsteadiness and had pronounced ataxia in all limbs. There was profound loss of proprioception to the shoulders in his arms with pseudoathetosis, with no corresponding lower limb involvement. Vibration …

A 35-year-old male developed sensory abnormality of peripheral limbs and oral cavity after prior infection with diarrhea and cold symptoms. Hyperrhinolalia, nasopharyngeal reflux, double vision, and wobbling in walking rapidly progressed. Neurological examination revealed palatoplegia, omnidirectional ophthalmoplegia, hyperreflexia, sensory disturbance of extremities, and truncal and limb ataxia due to decreased deep sensation. A peripheral nerve conduction study found a slight decrease in sensory nerve action potential of the median nerve and a decrease in F wave frequency of the median nerve. Serum IgM-CMV antibody was positive on admission. After IVIg therapy, palatoplegia and ataxia markedly improved. In this case, GalNAc-GD1a and GM2 antibodies, which are often detected after CMV infection, were positive in addition to the GT1a and GQ1b antibodies, and it was assumed that these findings were associated with the palatoplegia, which is included in cranial nerve palsy. Pathophysiologically, the present case is considered to be an overlap with acute oropharyngeal palsy (AOP), which is a rare subtype of Guillain-Barre syndrome, and Fisher syndrome (FS). The clinical aspects of the present case suggest a continuous spectrum between AOP and FS.

Background Neurodegenerative disorders are characterized by insidious progression with poorly-delineated long latent period. Antecedent clinical insult could rarely unmask latent neurodegenerative disorders. Here, we report an autopsy-proven case of corticobasal degeneration which was preceded by a lacunar infarction. Case presentation A 58-year-old man presented with acute ataxia associated with a lacunar infarction in the right paramedian pons. His ataxia persisted with additional progressive gait difficulty and left arm clumsiness. Six months later, a follow-up neurological examination showed asymmetrical bradykinesia, apraxia, dystonic posturing, postural instability, and mild ataxia of the left limbs. Cognitive examination revealed frontal executive dysfunction and visuospatial difficulties. Dopamine transporter imaging scan demonstrated bilateral reduced uptakes in mid-to-posterior putamen, more prominent on the right side. Levodopa-unresponsive parkinsonism, asymmetric limb dystonia, and ideomotor apraxia became more conspicuous, while limb ataxia gradually vanished. The patient became unable to walk without assistance after 1 year, and died 4 years after the symptom onset. Autopsy findings showed frontoparietal cortical atrophy, ballooned neurons, and phosphorylated tau-positive astrocytic plaques and neuropil threads with gliosis and neuronal loss, confirming the corticobasal degeneration. Conclusions The case illustrates that precedent clinical events such as stroke might tip a patient with subclinical CBS into overt clinical manifestations.

Background Bickerstaff’s brainstem encephalitis (BBE) and Fisher syndrome (FS) are immune-mediated diseases associated with anti-ganglioside antibodies, specifically the anti-GQ1b IgG antibody. These two diseases potentially lie on a continuous spectrum with Guillain-Barré Syndrome (GBS). There are some reports of family cases of GBS and fewer of FS. However, there are no reports of family cases of BBE and FS. Case presentation We report a familial case of an 18-year-old son who had BBE and his 52-year-old mother diagnosed with FS within 10 days. The son showed impaired consciousness 1 week after presenting with upper respiratory symptoms and was brought to our hospital by his mother. He showed decreased tendon reflexes, limb ataxia, albuminocytologic dissociation in his spinal fluid, and positive serum anti-GQ1b antibodies. Haemophilus influenzae was cultured from his sputum. He was diagnosed with BBE and treated with intravenous immunoglobulin (IVIg) therapy, which led to an improvement in symptoms. The mother presented with upper respiratory symptoms 3 days after her son was hospitalized. Seven days later, she was admitted to the hospital with diplopia due to limited abduction of the left eye. She showed mild ataxia and decreased tendon reflexes. Her blood was positive for anti-GQ1b antibodies. She was diagnosed with FS and treated with IVIg, which also led to symptomatic improvement. Conclusions There are no previous reports of familial cases of BBE and FS; therefore, this valuable case may contribute to the elucidation of the relationship between genetic predisposition and the pathogenesis of BBE and FS.

Background Cogan’s anterior internuclear ophthalmoplegia (INO) is characterized by INO with inability to converge and commonly thought to be due to rostral midbrain lesion. A lesion outside midbrain that causes unilateral Cogan’s anterior INO combined with upgaze palsy and ataxia are rarely described. Case presentation A 67-year old male presented with left Cogan’s anterior internuclear ophthalmoplegia (INO), left appendicular ataxia and bilateral upgaze palsy. A Magnetic Resonance Imaging (MRI) and Magnetic Resonance Angiography (MRA) brain showed a left dorsal tegmental infarct at the level of pontomesencephalic junction. Conclusions This case highlights the clinical importance of Cogan’s anterior INO in combination with upgaze palsy and ataxia, and report possible site of lesion in patients with such constellation. Clinicians should consider looking for cerebellar signs in cases of Cogan’s anterior INO, apart from just considering localizing the lesion at the midbrain.

A 69-year-old man was admitted to our hospital for progressive muscle weakness in both lower limbs and limb ataxia (day 0). Nerve conduction studies showed low compound muscle action potential amplitudes at rest and increased amplitudes after maximum voluntary contraction. Blood testing revealed SOX-1 antibodies. He was diagnosed with paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome (PCD-LEMS). He died from aspiration pneumonia on day 9. Small-cell lung carcinoma (SCLC), which had not been obvious on computed tomography, was found during the autopsy. Patients with PCD-LEMS who test positive for SOX-1 antibodies should be carefully evaluated for SCLC.

Background SYNE1 ataxia is an autosomal recessive hereditary condition, the main characteristic features of which are gait and limb ataxia and cerebellar dysarthria. Reports have revealed that the clinical phenotype of SYNE1 ataxia is more complex than the first published cases with pure cerebellar signs indicated. The aim of this study was to characterize eye movement alterations in the first diagnosed Hungarian SYNE1 ataxia patients. Results Saccades and antisaccades were examined with an eye tracker device in 3 SYNE1 (one patient has two frameshift mutations [c.8515_8516insA, p.Met2839Asnfs*53 and c.11594_11595insG, p.Glu3866*] in a compound heterozygous state, whereas two subjects have a splicing variant [c.23146-2A > G] in a homozygous state), 6 Friedreich ataxia (FA) patients and 12 healthy controls. Besides that, detailed clinical phenotyping and comprehensive neuropsychological assessment were carried out in all patients with ataxia. In addition to the characteristic cerebellar alterations, pyramidal signs and polyneuropathy were observed at least in 2 SYNE1 ataxia patients, for which no other underlying reason was found. The eye tracking assessment revealed hypometric saccades in the longer amplitude (18.4°) saccadic paradigm in all SYNE1 patients, whereas 2 out of 3 SYNE1 subjects performed slow saccades as well. In the antisaccade task, higher incorrect ratios of antisaccades were demonstrated in SYNE1 patients compared to healthy controls, showing inverse correlation with working memory test results. The corresponding data of FA patients was dispersed over a wide range, partially overlapping with control data. Conclusions The current study draws attention to the presence of eye movement disorders in patients with SYNE1 ataxia and demonstrates that alterations in the antisaccade paradigm may be related to working memory deficits.

Background Paraneoplastic cerebellar degeneration (PCD) is a devastating paraneoplastic syndrome that occasionally occurs in patients with Hodgkin lymphoma (HL). Anti-Ma2 is a well-characterized onconeuronal antibody and one of the causes of PCD. There has been only one previous report of anti-Ma2-associated paraneoplastic syndrome as a complication of HL. Here we present a rare case of anti-Ma2-associated PCD in a patient with nodular lymphocyte-predominant HL (NLPHL). Case presentation A 77-year-old man with a 3-month history of gait instability and a 2-month history of oscillopsia was referred to our hospital for further investigation. On examination, his cognition was normal. He had nystagmus in all directions of gaze; specifically, he had horizontal and rotatory nystagmus in the primary position, downbeat nystagmus after right, left, and up gaze, and upbeat nystagmus after down gaze. Although his limb ataxia was mild, his trunk ataxia was so pronounced that he was unable to walk without support. We strongly suspected paraneoplastic syndrome and tested for neuronal autoantibodies. The anti-Ma2 antibody was strongly positive in the blood and cerebrospinal fluid but other antineuronal autoantibodies were negative. Computed tomography showed an enlarged lymph node in the right axilla but no masses. Biopsy confirmed a diagnosis of NLPHL. The NLPHL cells stained with anti-Ma-2 antibody in the cytoplasm, suggesting these abnormal cells contained protein that was cross-reactive with Ma-2. Conclusions To the best of our knowledge, this is the first case of anti-Ma2-associated PCD in a patient with NLPHL that was confirmed using immunostaining of the lymph node tissue with anti-Ma2 antibody. Our case confirms an association between anti-Ma2-associated PCD and NLPHL.

A 52-year-old previously healthy man was hospitalized with a 6-day history of progressive gait instability rendering him unable to walk. He reported no respiratory symptoms or fever. He was a smoker (5–10 pack-years) and consumed an undisclosed amount of alcohol over weekends for some years. At presentation, he was tachypneic (20 bpm) and pyrexial (37.7°C) but alert and oriented. He exhibited cerebellar signs, including multidirectional gaze-evoked nystagmus, dysarthria, and truncal and appendicular ataxia. His examination was otherwise normal.

Introduction Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) is a rare symptom. Several studies have reported that a small brainstem lesion could cause WEBINO. Case report The authors present the case of an 88-year-old female individual who developed sudden-onset diplopia and gait disturbance. Neurological examination revealed WEBINO with convergence impairment, gaze-evoked upward nystagmus on upward gaze, and bilateral limb ataxia. Brain magnetic resonance imaging revealed a small paramedian pontine tegmentum infarction, responsible for the symptoms. A literature review of WEBINO in ischemic stroke revealed that most patients exhibited impaired convergence and other neurological symptoms. Conclusion Gaze-evoked upward nystagmus on upward gaze and bilateral limb ataxia accompanied by WEBINO due to a small brainstem lesion were the characteristic findings of our case.

A 26-year-old woman (patient 1 on the family tree—figure 1) gave a 6-year history of dysarthria, occasional jerks and progressive gait unsteadiness with frequent falls, and had become bedridden. On examination, she had dorsal kyphosis and pes cavus. There was severe truncal and appendicular ataxia, generalised action myoclonus, hyporeflexia, hypotonia and bilateral extensor plantar reflexes. Electromyography with nerve conduction studies identified a sensorimotor polyneuropathy, with intermediate conduction velocities. Figure 1 Family tree depicting genetic and phenotypic status of the family members. Her medical history was unremarkable, with a normal development. She had experienced one recent generalised tonic–clonic seizure. She had an older sister (patient 2 on the family tree—figure 1) with a rapidly progressive nephrotic syndrome starting at the age of 17, becoming steroid resistant and needing haemodialysis after a few months. She also had a normal development and unremarkable medical history. At age of 21, she had developed action myoclonus of the lower limbs, with subjective loss of strength and frequent falls, later progressing to the upper limbs. She started having generalised tonicclonic seizures and lost walking ability in the next year. At aged 28 years, she underwent renal transplantation and died 5 years later due to graft-related complications. Their parents were consanguineous (they were half-siblings) and they had a healthy sister. ### How can you localise her myoclonus and what should be the initial steps in the evaluation? Clinical assessment of pathological myoclonus requires a systematic approach. On neurological examination, it is important to note if the myoclonus appears at rest, on posture or during action. If present at rest, a spinal or brainstem source is more likely, whereas, if action induced, a cortical source should be suspected. Distribution is also important: cortical myoclonus is typically focal or multifocal, spinal segmental myoclonus can also be focal (but usually is stimulus sensitive and not action induced), while generalised myoclonus is generally subcortical (brainstem or propriospinal). Generalised myoclonus …

ObjectiveTo better characterize the neurologic and cognitive profile of patients with spinocerebellar ataxia 34 (SCA34) caused by ELOVL4 mutations and to demonstrate the presence of ELOVL4 cellular localization and distribution abnormalities in skin-derived fibroblasts.MethodsWe investigated a 5-generation French-Canadian kindred presenting with a late-onset cerebellar ataxia and recruited age- and education-matched controls to evaluate the presence of neurocognitive impairment. Immunohistochemistry of dermal fibroblasts derived from a patient's skin biopsy was performed.ResultsPatients had a late-onset slowly progressive cerebellar syndrome (mean age at onset 47 years; range 32–60 years) characterized by truncal and limb ataxia, dysarthria, hypometric saccades, and saccadic pursuits. No patient had past or current signs of erythrokeratodermia variabilis, which had previously been reported. MRI revealed cerebellar atrophy, with pontine atrophy (4 of 6 patients), and cruciform hypersignal in the pons (2 of 6 patients). Fluorodeoxyglucose-PET showed diffuse cerebellar hypometabolism in all 5 tested patients with subtle parietal hypometabolism in 3. Significant cognitive deficits were found in executive functioning, along with apparent visuospatial, attention, and psychiatric involvement. Immunohistochemistry of dermal fibroblasts showed mislocalization of the ELOVL4 protein, which appeared punctate and aggregated, supporting a dominant negative effect of the mutation on protein localization.ConclusionsOur findings support the pathogenicity of ELOVL4 mutations in cerebellar dysfunction and provide a detailed characterization of the SCA34 phenotype, with neurocognitive changes typical of the cerebellar cognitive-affective syndrome.

A 65-year-old man with a history of Wallenberg syndrome caused by vertebral artery dissection at 62 years old was admitted to our hospital with nausea, vertigo, right facial dysesthesia, right hemiplegia, crossed sensory disturbance (sensory loss and numbness in the right face and left body below the neck), and right limb ataxia. Magnetic resonance imaging (MRI) performed 80 minutes after onset revealed no acute ischemic stroke lesions, but magnetic resonance angiography (MRA) demonstrated complete occlusion of the right vertebral artery. Based on these neurological and MRA findings, atypical lateral medullary infarction was suggested, and intravenous tissue plasminogen activator (IV-tPA) was started 178 minutes after onset. Right hemiplegia improved immediately after IV-tPA administration. MRI performed on hospital day 2 showed an acute ischemic lesion on the right side of the medulla oblongata, resulting in a diagnosis of Opalski syndrome. Opalski syndrome is a rare subtype of Wallenberg syndrome accompanied by hemiplegia of the side ipsilateral to the lesion, and expansion of the stroke lesion to the corticospinal tract below the pyramidal decussation is considered to cause ipsilateral hemiplegia. Based on this case and previous reports, Opalski syndrome should be considered when limb ataxia and crossed sensory deficit are observed among patients with hyperacute-onset hemiplegia, and IV t-PA therapy should be considered even in the absence of neurological findings such as dysphagia, dysarthria, and Horner's signs and radiological evidence of acute ischemic stroke.

Abstract: The number of primary immune deficiencies exceeds 350, approximately a quarter of them having neurological implications. Severe central nervous system infections may occur in an even higher proportion. Beyond listing in a table of all diseases with a neurological impact, the author gives detailed analysis of one typical disorder. Ataxia telangiectasia is caused by biallelic mutation of the ATM gene resulting in genomic instability, increased cancer risk, immune deficiency and a predominantly cerebellar neurodegeneration. The most common classic form is characterized by gait and limb ataxia, oculomotor apraxia, choreoathetosis, disturbance of speech and swallowing, less often by other movement disorders. There is no remarkable cognitive deficit. Telangiectasia of the conjunctivae and skin usually appears after 6 years of age. Frequent, especially severe sino-pulmonary infections may indicate the immune deficiency present in 60 to 80% of patients, who are also prone to malignancies. The clinical course is sometimes atypical or has a late onset which results in diagnostic difficulties. Serum alpha-fetoprotein level is elevated in nearly all patients. Brain MRI shows progressive cerebellar atrophy starting at the age of 7–8 years. DNA testing of the ATM gene is necessary for the diagnosis. The detected biallelic pathogenic variants provide help for family planning and for possible gene therapies in the future. Ataxia telangiectasia has to be differentiated from a number of other disorders, some of which also belong to primary immune deficiencies. The disorder has no causal treatment at present, the patients live until their young adult ages. Orv Hetil. 2018; 159(49): 2057–2064.

The aim of this study was to describe five patients with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) with chronic cough and preserved limb muscle stretch reflexes. All five patients were in the seventh decade of age, their gait imbalance having been initiated in the fifth decade. In four patients cough antedated gait imbalance between 15 and 29 years; cough was spasmodic and triggered by variable factors. Established clinical picture included severe hypopallesthesia predominating in the lower limbs with postural imbalance, and variable degree of cerebellar axial and appendicular ataxia, dysarthria and horizontal gaze-evoked nystagmus. Upper- and lower-limb tendon jerks were preserved, whereas jaw jerk was absent. Vestibular function testing showed bilateral impairment of the vestibulo-ocular reflex. Nerve conduction studies demonstrated normal motor conduction parameters and absence or severe attenuation of sensory nerve action potentials. Somatosensory evoked potentials were absent or severely attenuated. Biceps and femoral T-reflex recordings were normal, while masseter reflex was absent or attenuated. Sympathetic skin responses were normal. Cranial MRI showed vermian and hemispheric cerebellar atrophy predominating in lobules VI, VII and VIIa. We conclude that spasmodic cough may be an integral part of the clinical picture in CANVAS, antedating the appearance of imbalance in several decades and that sparing of muscle spindle afferents (Ia fibres) is probably the pathophysiological basis of normoreflexia.

Midbrain infarction causing oculomotor nerve palsy with contralateral ataxia is named Claude's syndrome. Herein we report the case of a variant of Claude's syndrome, which shows pupil-sparing oculomotor nerve palsy without the accompanying neurological deficits other than subtle truncal ataxia. MRI and Diffusion Tensor Imaging revealed that midbrain infarction was located rostrally above the decussation of the superior cerebellar peduncle (SCP) and might have partially destructed the tectospinal tract, which resulted in the absence of limb ataxia and presence of subtle truncal ataxia. In this variant of Claude's syndrome, we should carefully assess truncal ataxia to avoid misdiagnosing it as isolated pupil-sparing oculomotor nerve palsy because the patient showed apparently normal gait and truncal ataxia was only revealed by unstable tandem gait.

A 40-year-old woman with chronic gastritis who did not have alcoholism had lost 50 pounds in the past 45 days and presented with dyscoordination and diplopia. Examination showed confabulation, ophthalmoplegia, nystagmus, and appendicular ataxia. Brain MRI (Figure) showed diffusion-weighted imaging and fluid-attenuated inversion recovery abnormalities suggestive of Wernicke encephalopathy (WE). With classic triad of WE and MRI findings, IV thiamine 500 mg TID was administered for 3 days, followed by maintenance oral thiamine. The patient showed substantial improvement. Thiamine replacement therapy should be considered in patients with malnutrition or malabsorption as it is important in maintaining cellular osmotic gradients. Thiamine deficiency may lead to cytotoxic edema, especially in high metabolic demand regions such as thalami and mammillary bodies.1

Background and Purpose: Strokes due to small (Methods: This study is a retrospective analysis of clinical and imaging features of a prospectively assessed series of 108 consecutive patients with acute cerebellar infarction admitted to Liverpool Hospital, Sydney, NSW, Australia, during 2011–2015. Results: The mean age of the patients was 67 years, and 33 (31%) had small cerebellar infarction. Compared to large cerebellar infarction, those with small cerebellar infarction had a comparable distribution of vascular risk factors but significantly less nausea and vomiting, gait disturbance, limb ataxia, and dysarthria. The posterior (n = 22, 67%) lobe was most commonly affected, followed by the anterior (n = 9, 27%) and flocculonodular (n = 2) lobes. Dizziness, limb ataxia, and nystagmus were significantly more common in patients with anterior lobe infarction. Vertebrobasilar disease was the presumed aetiology in 40 patients (37%), and was less commonly seen in small as compared to large cerebellar infarction. Cardioembolism affected 37% of the patients, irrespective of the size or topography of the cerebellar infarction, and there was no relation of supratentorial white matter lucencies (WMLs) to the size of cerebellar infarction. At 3 months, 65% of the patients were functionally independent (according to modified Rankin Scale scores of 0–2), and having a poor outcome was significantly related to moderate-to-severe supratentorial WML and large cerebellar infarction. Conclusions: Small cerebellar infarction accounted for one-third of the ischaemic strokes in this location, most often involved the posterior lobe, causing fewer clinical features, and had a better clinical outcome than large cerebellar infarction. Patients with small cerebellar infarction require appropriate vascular management including investigation for a cardioembolic source.

Background Bickerstaff's brainstem encephalitis (BBE) is characterized by acute ophthalmoplegia, ataxia and impaired consciousness. Serum anti-GQ1b antibody in the acute phase has been detected in many BBE cases. Posterior reversible encephalopathy syndrome (PRES) is characterized by acute neurological symptoms with vasogenic edema in the bilateral parieto-occipital regions. It has been pointed out that the activation of inflammatory cytokines might be involved in the pathophysiology of PRES and BBE. Case presentation A 37-year-old woman had an upper respiratory infection a week before losing consciousness. On admission, she was in a coma and her blood pressure was 134/96 mmHg. Doll's eye phenomenon was negative. Bilateral tendon reflexes were normal, although Babinski signs were bilateral positive. Cerebrospinal fluid examination showed normal protein concentration and cell counts. Brain magnetic resonance imaging findings were normal. We administered intravenous methylprednisolone therapy (1000 mg/day), acyclovir (1500 mg/day) and fosphenytoin sodium hydrate (22.5 mg/kg/day). Brain magnetic resonance imaging on the third admission day showed an increased apparent diffusion coefficient map, and high intensities in diffusion-weighted imaging in the bilateral occipital cortex and subcortex, which are consistent with PRES. Nerve conduction studies were normal. The patient was treated with intravenous immunoglobulin therapy (0.4 g/kg/day) from the fourth admission day. Her consciousness level rapidly improved, and we were able to detect obvious ophthalmoplegia and limb ataxia. Diffusion-weighted imaging was improved on the 13th day of admission. Serum anti-GQ1b immunoglobulin G antibody on admission was positive. We ultimately diagnosed her with BBE. Conclusions We reported a rare case of BBE complicated with PRES.

Objectives: Neuroimaging is contributing to the rising costs of dizziness evaluation. This study examined the rate of central neurological causes of dizziness, relevant clinical predictors, and the costs and diagnostic yields of neuroimaging in dizziness assessment. Methods: We retrospectively reviewed the records of 521 adult patients who visited the hospital during a 12-month period with dizziness as the chief complaint. Clinical findings were analyzed using Fisher’s exact test to determine how they correlated with central neurological causes of dizziness identified by neuroimaging. Costs and diagnostic yields of neuroimaging were calculated. Results: Of the 521 patients, 1.5% had dizziness produced by central neurological causes. Gait abnormalities, limb ataxia, diabetes mellitus, and the existence of multiple neurological findings predicted central causes. Cases were associated with gait abnormalities, limb ataxia, diabetes mellitus, and the existence of multiple neurological findings . Brain computed tomography (CT) and magnetic resonance imaging (MRI) were performed in 42% and 9.5% of the examined cases, respectively, with diagnostic yields of 3.6% and 12%, respectively. Nine cases of dizziness were diagnosed from 269 brain scans, costing $607 914. Conclusion: Clinical evaluation can predict the presence of central neurological causes of dizziness, whereas neuroimaging is a costly and low-yield approach. Guidelines are needed for physicians, regarding the appropriateness of ordering neuroimaging studies. Abbreviations: OR: odds ratio; CI: confidence interval; ED: emergency department; CT: computed tomography; MRI: magnetic resonance imaging; HINTS: Head impulse, Nystagmus, Test of skew

Progressive multifocal leukoencephalopathy (PML) is a rare, opportunistic and often fatal disease of the CNS which may occur under immunosuppression in transplant patients. Brain stem PML is associated with a particularly bad prognosis. Here, we present a case of a renal transplant patient treated with mycophenolate mofetil (MMF) and tacrolimus who developed brain stem PML with limb ataxia, dysarthria and dysphagia. Diagnosis was established by typical MRI features and detection of JCV-DNA in the CSF. Immune reconstitution after stopping MMF and tacrolimus led to a complete and sustained remission of symptoms with improvement of the brain stem lesion over a follow-up over 20months. In summary, early detection of PML and consequent treatment may improve neurological outcomes even in brain stem disease with a notorious bad prognosis.

Posterior inferior cerebellar artery (PICA) aneurysm is relatively rare. We report on a 74-year-old woman presenting with dizziness and right-side tilted gait caused by a right-side distal PICA aneurysm, which mimicked a right lateral medullary infarction. A neurological examination showed right-side limb ataxia and left-beating torsional nystagmus, similar to a right lateral medullary infarction. Magnetic resonance imaging revealed a distal PICA aneurysm in the right-side middle cerebellar peduncle region.

Introduction X-linked adrenoleukodystrophy (X-ALD) encompasses several clinical and neuroimaging phenotypes, including cerebral X-ALD, the most common phenotype in children, and adrenomyeloneuropathy, the most common phenotype in adults. A spinocerebellar variant of X-ALD has been described in individuals from the Far East, but the criteria for its diagnosis are unclear. Case report A 35-year-old man from Albania was assessed because of a familial, slowly progressive spastic-ataxic gait associated with neurogenic bladder, sexual dysfunctions, and manic-like behavior. There was no definite clinical feature that suggested cerebellar involvement (eg, cerebellar limb ataxia, nystagmus, and dysarthria). A few months earlier, he had received a diagnosis of Addison disease. Brain magnetic resonance imaging showed a leukoencephalopathy with predominant cerebellum and brainstem involvement, and FDG-PET revealed marked cerebellar hypometabolism. The diagnosis of X-ALD was made because we found an increase of very long chain fatty acids, and a new ABCD1 mutation (c.1627C>T, p.Pro543Ser). Conclusions X-ALD should be included in the differential diagnosis of adult leukoencephalopathies with predominant involvement of infratentorial structures, that is, the cerebellum and brainstem. From a classification perspective, our patient (of white origin), like others (all of Asian origin), should be considered as suffering from a variant of adrenomyeloneuropathy rather than from spinocerebellar X-ALD. Actually, the term "spinocerebellar" or similar ones, such as "cerebello-brainstem dominant form," should be limited to those exceptional cases, in which both the clinical and neuroimaging findings point exclusively (or at least predominantly) to the involvement of infratentorial structures.

Pathological yawning is rarely observed in cerebral or spinal diseases. A 67-year-old woman was admitted with a seven-day progressive hemisyndrome with left-sided limb ataxia and hypesthesia. The patient yawned with a high frequency, partially in salve-like episodes. MRI showed a cervical myelitis over more than three vertebral segments up to the lower medulla and Aquaporin-4-antibodies were positive (diagnostic criteria for a Neuromyelitis optica spectrum disorder were fulfilled). Under treatment with methylprednisolone, followed by plasmapheresis and immunoadsorption, clinical symptoms were regressive and the frequency of yawning completely normalized. When observing pathological yawning, even in the absence of other cerebral or brainstem symptoms, one should be aware of NMOSD as a possible cause.

Background CAPOS (Cerebellar ataxia, Areflexia, Pes cavus, Optic atrophy and Sensorineural hearing loss) syndrome is caused by the heterozygous mutation, c.2452G > A, in the ATP1A3 gene. Other mutations in this gene can cause a spectrum of overlapping phenotypes including alternating hemiplegia of childhood, rapid onset dystonia parkinsonism, early infantile epileptic encephalopathy and fever induced paroxysmal weakness and encephalopathy. The phenotype is still mistaken for mitochondrial/metabolic disorders and follow up studies are scare. Case presentation We report a 20 year old Norwegian male with ataxia, sensorineural deafness and visual loss. Before the age of five he experienced three fever related episodes of acute neurological deterioration when he temporarily lost his acquired motor skills and developed persistent gait and limb ataxia. In childhood, he developed bilateral optic atrophy and bilateral sensorineural hearing loss. Motor skills improved and at age 20 the patient showed a mild ataxia, hearing loss and reduced vision. A c.2452G > A mutation in the ATP1A3 gene was identified and CAPOS syndrome was confirmed. Conclusions This is the first Norwegian patient reported with CAPOS syndrome. Our patient had a de novo, previously identified ATP1A3 mutation. The combination of recurrent episodes of fever related ataxia, loss of motor skills in early childhood, and early onset hearing and vision loss is typical of CAPOS syndrome. Previous reports suggest a gradual progression of the disease after the initial episodes, while this patient showed a good outcome with improvement of motor skills from adolescence long after the last deterioration episode. Electronic supplementary material The online version of this article (10.1186/s40673-019-0096-3) contains supplementary material, which is available to authorized users.

Purpose of review:To identify the different indications for the treatment of neurologic disorders with the potassium channel blockers 4-aminopyridine (4-AP) and 3,4-diaminopyridine (3,4-DAP).Recent findings:4-AP is an effective symptomatic treatment for downbeat nystagmus (DBN), episodic ataxia type 2 (EA2) (5–10 mg TID), and impaired gait in multiple sclerosis (MS) (10 mg BID). 3,4-DAP (5 mg/d–20 mg TID) improves symptoms in Lambert-Eaton myasthenic syndrome (LEMS) (randomized placebo-controlled trials for all 4 entities). 4-AP may also be effective in cerebellar gait ataxia of different etiologies (2 case series), upbeat nystagmus, and limb ataxia in MS (single cases). In the recommended dosages, they are well tolerated. The assumed mode of action is a blockade of mainly Kv1.5: in DBN, this increases the excitability of Purkinje cells (PC), and in EA2, restores the precision of resting discharge of PC. In MS, 4-AP improves the conduction of action potentials in demyelinated axons, and in LEMS, 3,4-DAP facilitates the transmission at the neuromuscular endplate by prolonging the action potential duration.Summary:There is sufficient evidence that APs are indicated for the symptomatic treatment of DBN, EA2, gait ataxia due to MS and cerebellar disorders, and LEMS with a reasonable risk-benefit profile.

We identified PNKP mutations in a Norwegian woman with AOA. This patient had the typical findings with cognitive dysfunction, peripheral neuropathy, cerebellar dysarthria, horizontal nystagmus, oculomotor apraxia, and severe truncal and appendicular ataxia. In addition, she had hypoalbuminemia and massive lower limb edema which showed some improvement with treatment. Exome sequencing identified two heterozygous mutations, one in exon 14 (c.1196T>C, p.Leu399Pro) and one in exon 16 (c.1393_1396del, p.Glu465*). This is the first non-Portuguese patient with AOA due to PNKP mutations and provides independent verification that PNKP mutations cause AOA. publishedVersion

Anti-IgLON5-syndrome is known to be an antibody-mediated disease that mainly affects central structures in tegmentum and hippocampus and leads to associated symptoms like sleep-related disturbances, parkinsonism, chorea and limb ataxia. This is the first case of a patient with anti-IgLON5-syndrome and generalized fasciculations and neuromyotonic discharges in electromyography, suggesting that a peripheral involvement may occur in anti-Ig-Lon5-syndromes.

Autosomal-recessive spinocerebellar ataxia type 18 (SCAR18) is a rare neurologic disorder. It is caused by bi-allelic aberrations in the GRID2 gene, encoding an ionotropic glutamate receptor. In total, 20 affected individuals with mainly homozygous/compound heterozygous intragenic deletions/duplications, two different missense variants and one nonsense variant in GRID2 have been reported, so far. SCAR18 is characterized by delayed psychomotor development, intellectual disability, severely impaired gait due to cerebellar ataxia, ocular movement abnormalities, and cerebellar atrophy in brain imaging. By trio exome sequencing, we now identified a novel homozygous nonsense variant (c.568C > T; p.Gln190*) in GRID2 in a four year old female from a consanguineous family who presented with a particularly severe manifestation of SCAR18. The girl was born after an uneventful pregnancy and showed early-onset, profoundly delayed psychomotor development with no achieved psychomotor milestones at age 4 years. Additionally, she presented with severe muscular hypotonia, progressive truncal and appendicular ataxia, binocular vertical nystagmus, central hearing loss and incomplete loss of sight. She was dystrophic, interacted only very little and had behavioral anomalies such as eating hair and bruxism. Brain imaging showed cerebellar hypoplasia, extended cerebrospinal fluid spaces and beginning reduction of cerebral volume. Our findings further delineate the mutational and clinical spectrum of GRID2-associated spinocerebellar ataxia type 18 and indicate that homozygous nonsense variants are possibly associated with the severe end of the SCAR18 phenotypic spectrum.

espanolEl sindrome opsoclonus-mioclonus es una condicion rara, asociada con una etiologia de caracter autoinmune, tanto paraneoplasica, parainfecciosa o idiopatica. Estos pacientes se presentan con ataxia del tronco y extremidades, con caidas, opsoclonus, mioclonias, y se puede acompanar de diversos grados de encefalopatia, signos cerebelosos y alteraciones del sueno. En el caso de la poblacion pediatrica, se debe evaluar por neuroblastoma; y en adultos con encefalopatia asociada se debe realizar una evaluacion exhaustiva para detectar malignidad oculta. Mientras que los sintomas neurologicos agudos pueden controlarse mediante inmunoterapia, y se ha visto respuesta parcial a tratamiento antitumoral, el resultado a largo plazo se caracteriza por la presencia de deficit neuropsicologico. EnglishThe opsoclonus-myoclonus syndrome is a rare medical condition associated with an autounmmune etiology, it can be paraneoplasic, parainfectios or idiopatic. The patients present with truncal and limb ataxia, falls, opsocolunus and myoclonus. Also they could present a certain degree of encephalopathy, cerebelar damage signs and sleep disturbances. In the case of the pediatric population an evaluation for neuroblastoma must be done; in adults presenting with encephalopathy a complete evaluation must be done looking an underlying neoplasia. The acute neurological symtomps can be controlled with immunotherapy and there have been a partial response to the antitumoral medication, but the long term outcome is characterized for the presence of neuropsicological deficit.

The severity of appendicular ataxia is currently assessed by neurological specialists observing the motor deficits during the performance of bedside tests. These tests are traditionally restricted to discrete subjective scales and prescribed by constraints that may in turn affect the subject's performance. To overcome these limitations and facilitate uniform monitoring of cerebellar ataxia, an instrumented assessment system using a wearable sensor has been developed for the rhythmic finger and foot tapping tasks. Departing from the conventional obligation to spatiotemporal parameters that are described clinically, the proposed approach investigates features based on information theory to evaluate the variability of the tapping dynamics. From a clinical trial of 24 healthy subjects and 34 patients diagnosed with cerebellar ataxia (CA), the findings revealed not only are there more variations in movement patterns and timing of tapping events in CA but that movement complexity was also degraded across multiple entropy scales. The system using combined models of different features was able to achieve an average classification accuracy of 81% and 79% in finger and foot tapping respectively. The outcomes strongly agreed with the clinical scale widely-used for the assessment and rating of ataxia (SARA) to a correlation level of 0.71 (p