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IntroductionRapidly progressive dementias (RPD) are conditions that develop over days, weeks or months, which could be treatable if diagnosed in the acute phase.Clinical caseA 62-year-old man with personal history of type 2 diabetes, started complaining of fronto-temporal headache, nausea and sub-febrile temperature. He went to his family doctor who prescribed ciprofloxacin 500 mg bid. Later on, he had difficulty to sleep and referred complex visual hallucinations. His family noted involuntary movements of the left upper limb and that he became more clumsy needing help for daily life activities. He went to our hospital one week later. He was apyretic and hemodynamically stable. On neurological examination, he had executive and visuospecial dysfunction, left limbs bradykinesia and ipsilateral limb ataxia. Involuntary movements of his left upper limb resembled alien limb phenomena. Complete blood count, complete metabolic panel, iron, folic acid, vitamin B12, anti-neuronal antibodies were normal. HIV, hepatitis B and C serologies were negative. Cerebrospinal fluid study showed 4 cells (100% mononuclear), normal glucose and protein levels, negative bacteriological exam but positive Herpes Simplex-1 Virus (HSV) DNA. Brain CT and MRI showed signs of ischemic microangiopathic leukoencephalopathy. He started treatment with acyclovir 30 mg/kg/d IV and quetiapine 100 mg id. His symptoms improved but he remained with a mild mnesic cognitive deficit and bradykinesia that stayed stable 3 years later.ConclusionThis case exemplifies atypical HSV-1 encephalitis, one cause of RPD, that an early recognition is essential to reduce its associated morbidity.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Sirs: The diagnosis of a patient with an early-onset cerebellar ataxia still remains a neurological challenge. Although this clinical syndrome merits careful and intensive evaluation, it frequently turns out to be a disappointing effort, for both patient and physician, in terms of understanding the underlying pathogenesis. The differential diagnosis is extensive and encompasses mostly metabolic and molecular-genetic disorders or yet unexplained syndromal diagnoses, most in a presumably autosomal recessive mode of inheritance. However, structural, neoplastic, and infectious posterior fossa lesions, some of which are potentially treatable, should be considered as well. Here, we describe a patient who presented with an early-onset progressive spinocerebellar syndrome, which was found to be caused by a central nervous system (CNS) localisation of Langerhans’ cell histiocytosis (LCH). This neurological syndrome was the presenting manifestation of the disease. A 23-year-old male was referred to our outpatient clinic because of progressive cerebellar ataxia. His medical history revealed a chronic bronchitis. He had always been clumsy in primary school sports. However, at the age of 8 years he noticed double vision in all directions. Four years later, gait difficulties and disturbances in fine motor tasks gradually evolved. The gait instability resulted in a suspension from his high school because of suspected drug abuse. Symptoms turned out to be progressive, and speech and swallowing difficulties developed subsequently. At the age of 18 years he lost the ability to run. From the age of 22 years, the severe gait disorder necessitated the use of a wheelchair outdoors. His parents were non-consanguineous and the family history was non-contributory. He started smoking cigarettes 4 years before referral and had a cumulative consumption of 5 pack years. Neurological examination revealed slight euphoria, normal cognitive functions, normal optic discs, saccadic intrusions and gazeevoked nystagmus in ocular pursuit, slowing of saccades, horizontal diplopia, cerebellar dysarthria, slowing of rapidly alternating tongue movements, impaired finger tapping, severe gait ataxia, moderately severe limb ataxia, absence of Romberg’s sign, no sensory abnormalities, and brisk tendon reflexes, without pathological reflexes. Scoliosis and skin abnormalities were absent. Laboratory examination, including vitamin E, ceruloplasmin, alpha-fetoprotein levels, lysosomal enzymes, lipid profile, organic acids, aminoacids, long-chain fatty acids, urinary bile alcohols, purines/pyrimidines, and angiotensin-converting enzyme, was without abnormalities. Mutationanalysis of the X25 gene failed to detect GAA-repeat expansions, making Friedreich’s ataxia highly unlikely. In addition, no abnormalities were found in the cerebrospinal fluid analysis, on electromyography or in nerve conduction studies, brainstem auditory evoked potentials, muscle biopsy, and ophthalmologic evaluation. During admission, polydypsia was observed and, in combination with a high-normal sodium level (146 mmol/L), diabetes insipidus was suspected. A thirst provocation test confirmed this diagnosis. Furthermore, endocrine evaluation revealed the presence of subclinical ACTH and growth hormone deficiency. Cranial magnetic resonance imaging (MRI) indicated a thickened, contrast-enhanced infundibulum; atrophy of the cerebellar vermis (Fig. 1a); and, on the T2-weighted images, asymmetrically distributed patchy areas of relative hyperintensity in the pons (Fig. 1b) that showed no enhancement after the administration of gadolinium. At this stage, the combination of a progressive spinocerebellar ataxia and diabetes insipidus, together with the findings on neuroimaging, left only a few differential diagnostic possibilities, including LCH, neurosarcoidosis, and a low-grade glioma. High Resolution computed tomography (HRCT) of the thoracic cavity showed discrete reticular interstitial opacities, predominantly affecting the apical zones. A bronchoalveolar lavage (BAL) showed five percent CD1 a and S100 immunopositive (Langerhans’) cells. A diagnosis of Langerhans’ cell histiocytosis with pulmonary and CNS involvement was made. Skeletal bone scintigraphy and radiographs, iliac crest bone marrow aspirate, and abdominal CT did not demonstrate other LCH localisations. The patient was treated with cranial radiation (20 Gray in 10 fractions), but despite this treatment the clinical course remained slowly progressive. Repeat neuroimaging showed identical non-progressive fossa posterior abnormalities. The diabetes insipidus was LETTER TO THE EDITORS

An outbreak of enzootic ataxia among sheep raised in the northeastern region of Brazil is described. Copper (Cu) deficiency was diagnosed in a herd of 56 sheep, among which five presented characteristic clinical symptoms of enzootic ataxia. The symptoms began 30 days after birth, with a clinical condition that included locomotion difficulty, limb ataxia, tremors, and continual falls. Liver biopsies were performed and blood was collected to determine hepatic and plasmatic Cu, iron (Fe), and zinc (Zn) concentration, respectively. The laboratory results showed that the animals presented low copper concentrations in the plasma and liver, without difference between the clinically healthy animals and those affected by enzootic ataxia. Even after supplementation with adequate Cu levels had been recommended, it was found on a new visit to the farm four months later that one animal still presented a clinical condition and that the hepatic Cu levels of the herd had not risen. Despite the low copper content of the diet, the high hepatic Fe levels found suggest that antagonism due to this element may have been an important factor in triggering copper deficiency in these animals, and thus, additional copper supplementation may be necessary for these animals.

We report a Japanese breath-hold diver (Ama) who presented neurological disorders after diving. He repeated diving into 25-30 meters depth in the sea for 6 hours. After diving, he felt dizziness and unsteady gait. Neurological examination showed left quadrant hemianopia, bilateral limb ataxia and ataxic gait. Head CT revealed gas bubbles in the left parietal lobe. In CT scan on 3 days after onset, gas bubbles disappeared and low density areas were observed in the bilateral parietal lobes. Brain imaging (DWI, T(2)WI and FLAIR) demonstrated high intensity in the parieto-occipital lobes. Neither pulmonary barotrauma nor intracardiac shunt was detected. He was diagnosed as having neurological decompression illness and therefore underwent hyperbaric oxygen therapy. The pathogenesis of this case was considered to be microbubbles induced by decompression. The present case suggests that repetitive rapid surfacing from the deep sea causes neurological decompression illness even in the breath-hold diver.

Background: Spinocerebellar ataxia type 2 (SCA2) is an autosomal-dominant hereditary ataxia characterized by progressive gait and limb ataxia, dysarthria, slow saccades, neuropathy and dementia. The expansion of trinucleotide CAG repeats in the coding region of the ATXN-2 gene leads to expanded polyglutamine stretch in the mutated protein which causes neuronal death. Objective: In this study, we investigated the blood plasma of SCA2 patients to find protein biomarkers. Methods: Thirty-two ataxia patients clinically suspected for SCA2 were evaluated by the International Co-operative Ataxia Rating Scale followed by genetic analysis using PCR. Plasma proteomics of SCA2 patients and age- and gender-matched healthy controls was done using 2D-difference in-gel electrophoresis, LC-MS/MS and Western blot. Results: Genetic analysis confirmed 10 of 32 suspected SCA2 patients. Proteomic data revealed nine differentially expressed proteins in SCA2. These proteins find good association with oxidative stress, calcium-dependent apoptosis, neuropathy, and cognitive impairment in SCA2 patients. Interestingly, the elevated levels of the voltage-dependent calcium channel γ-3 subunit showed a direct correlation with calcium-generated apoptosis of Purkinje cells. The cognitive deficit, a common symptom in SCA2 patients, seems to correlate with decreased levels of transthyretin and retinol-binding protein-4. Conclusions: Some of these identified proteins in SCA2 can be useful for therapeutic, diagnostic and prognostic purposes.

Objective To report a rare case of the coexistence of 2 spinocerebellar ataxia (SCA) mutations in a single patient. Design Case report. Setting University hospital, Movement Disorders Center. Patient A 54-year-old man of Mexican, American Indian, and French descent with an 11-year history of gait and limb ataxia. Main Outcome Measures Findings of clinical examination, magnetic resonance imaging, and video electroencephalographic monitoring. Results Neurologic history revealed a gradually progressive gait and limb ataxia along with muscle cramps and sensory symptoms in his distal extremities; examination revealed executive dysfunction, dysarthria, ataxia, and sensory neuronopathy. Episodes of loss of awareness were reported, but electroencephalograms were negative. Brain imaging demonstrated severe cerebellar and brainstem atrophy. Genetic evaluation of the case revealed mutations in both the SCA2 and SCA10 genes. Conclusion Our patient has a unique combination of genetic mutations for 2 different SCAs, types 2 and 10, which to our knowledge, has not been previously reported. His clinical phenotype is largely consistent with SCA2, but his possible seizures and Mexican heritage suggest influences of SCA10.

The spinocerebellar ataxias (SCAs) are a group of genetically heterogeneous neurodegenerative diseases characterized by limb ataxia with impaired balance, gait and eye movements. Either identified genetic mutations or suspected loci define the specific spinocerebellar ataxia (36 and counting) and each may have additional neurological features including cognitive impairment, seizure or pyramidal signs1. Spinocerebellar ataxia type 8 (SCA8) is a dominantly inherited mutation of chromosome 13q21 with a CTG•CAG expansion that is transcribed in both directions causing mutations in both ATXN8 and ATXN8OS (coding for Ataxin-8 and a noncoding sequence respectively). Spinocerebellar ataxia type 8 is an adult onset ataxia characterized by scanning dysarthria, gait and limb ataxia, hyperreflexia and variable eye movement abnormalities2. We describe here a patient with prominent oromandibular and lingual dystonia due to spinocerebellar ataxia type 8; these features have not been previously associated with spinocerebellar ataxia type 8. Oromandibular dystonia (OMD) often associated with lingual dystonia is a focal dystonia of either involuntary jaw opening or closure. Oromandibular dystonia especially with the presence of lingual dystonia can lead to dysarthria as well as chewing and swallowing problems. Patients with oromandibular dystonia may have a sensory trick such that placing an item in the mouth like a straw may reduce the involuntary movements thereby improving articulation, chewing or swallowing. Oromandibular dystonia can be a primary focal dystonia or secondary to disorders such as Wilson’s disease, neuroacathocytosis, Huntington disease or brainstem and basal ganglia lesions3. A 66 year old woman with a twenty year history of gait instability and 18 year history of dysarthria was referred to the Movement Disorders Clinic after four years of markedly worsening speech. Examination revealed dysarthria with excessive jaw opening accompanied by tongue protrusions while speaking. Jaw opening and speech improved by placing a dowel rod in her mouth. She also had wide based unstable gait, limb ataxia, hyperreflexia and ocular overshoot with sustained horizontal nystagmus and fine upbeat nystagmus on upgaze. She was much more affected by the oromandibular dystonia than the ataxia (Video). Strength and cognitive function were normal. There was no family history of similar illness or other movement disorders. Investigations including CSF, autoimmune serologies, blood smear and vitamins B12 and E were normal. Brain MRI revealed prominent atrophy of the cerebellar vermis and hemispheres without any other lesion (Figure 1). Genetic testing demonstrated a mutation of ATXN8 with 106 CTG repeats on the abnormal allele and 24 on the normal allele (normal

Acute cerebellar ataxia and acute cerebellitis represent a process characterized by parainfectious, postinfectious, or postvaccination cerebellar inflammation. There is considerable overlap between these entities. The mildest cases of acute cerebellar ataxia represent a benign condition that is characterized by acute truncal and gait ataxia, variably with appendicular ataxia, nystagmus, dysarthria, and hypotonia. It occurs mostly in young children, presents abruptly, and recovers over weeks. Neuroimaging is normal. Severe cases of cerebellitis represent the other end of the spectrum, presenting with acute cerebellar signs often overshadowed by alteration of consciousness, focal neurological deficits, raised intracranial pressure, hydrocephalus, and even herniation. Neuroimaging is abnormal and the prognosis is less favorable than in acute cerebellar ataxia. Acute disseminated encephalomyelitis may be confused with acute cerebellitis when the clinical findings are predominantly cerebellar, but lesions on neuroimaging are usually widespread. Paraneoplastic opsoclonus-myoclonus syndrome is often initially misdiagnosed as acute cerebellar ataxia, but has very specific features, course, and etiopathogensis.

In this article, we describe a 14-year-old boy with a confirmed diagnosis of Friedreich ataxia who underwent cardiac transplantation for left ventricular failure secondary to dilated cardiomyopathy with restrictive physiology. His neurological status prior to transplantation reflected early signs of neurological disease, with evidence of dysarthria, weakness, mild gait impairment, and limb ataxia. We review the ethical issues considered during the process leading to the decision to offer cardiac transplantation.

Objective: To characterize the phenotype of spinocerebellar ataxia type 36 (SCA36), a novel dominant disorder (nicknamed “Asidan”) caused by a hexanucleotide GGCCTG repeat expansion in intron 1 of the NOP56 gene. Methods: We investigated the clinical, genetic, and neuropathologic characteristics of 18 patients with SCA36. We performed histologic evaluation of a muscle biopsy specimen from 1 patient with SCA36, and neuropathologic evaluation of an autopsied brain from another patient with SCA36. Results: The (GGCCTG)n expansion was found in 18 ataxic patients from 9 families. The age at onset of ataxia was 53.1 ± 3.4 years, with the most frequent symptoms being truncal ataxia (100% of patients), ataxic dysarthria (100%), limb ataxia (93%), and hyperreflexia (79%). Tongue fasciculation and subsequent atrophy were found in 71% of cases, particularly in those of long duration. Skeletal muscle fasciculation and atrophy of the limbs and trunk were found in 57% of cases. Lower motor involvement was confirmed by EMG and muscle biopsy. The neuropathologic study revealed significant cerebellar Purkinje cell degeneration with obvious loss of lower motor neurons. Immunohistochemical analysis showed that NOP56 was localized to the nuclei of various neurons. Cytoplasmic or intranuclear inclusion staining of NOP56, TDP-43, and ataxin-2 was not observed in the remaining neurons. Conclusions: This is the first description of the unique clinical features of SCA36, a relatively pure cerebellar ataxia with progressive motor neuron involvement. Thus, SCA36 is a disease that stands at the crossroads of SCA and motor neuron disease.

Twenty-four hours after surgery for acute aortic dissection, a 51-year-old man with alcoholism developed agitation, decreased consciousness, mutism, and upbeat nystagmus on upward gaze. He also showed left-sided weakness with pyramidal signs and spastic limb ataxia. After 4 weeks treatment with

We have recently mapped the spinocerebellar ataxia type 28 (SCA28) locus on chromosome 18p11.22 in a four-generation Italian family. The clinical phenotype in affected individuals of this family was characterized by juvenile onset, slowly progressive gait and limb ataxia, dysarthria, hyperreflexia at lower limbs, nystagmus, and ophthalmoparesis. The mean age at onset was 19.5 years, and no evidence of anticipation between generations was observed. The disease locus on chromosome 18p11.22-q11.2 was found to span a region of 7.9 Mb of genomic DNA. Direct sequencing of candidate genes within the critical interval led to the identification of a heterozygous point mutation in one of them. The mutation was located in a highly conserved domain with proposed functional properties in the protein product of the SCA28 gene, and segregated with the disease phenotype in all affected members of this family. Further genetic screening in 105 patients with autosomal dominant spinocerebellar ataxia negative for mutations in known SCA genes allowed the identification of a distinct missense mutation in a second Italian family. Both mutations are associated with amino acid changes in evolutionarily conserved residues of the alleged SCA28 gene, and indicate SCA28 as the sixth recognized SCA genotype caused by point mutations.

Spinocerebellar ataxia-type 17 (SCA17) is an autosomal dominant cerebellar ataxia with a complex and variable phenotype characterized by ataxia, dementia, chorea, dystonia, and parkinsonism. Affected patients typically present in early or middle adulthood (mean age 33 years) with progressive gait and limb ataxia which is usually accompanied by dementia, psychiatric symptoms, and variable extrapyramidal features. Additional symptoms and signs such as hyperreflexia, saccadic slowing, akinesia, mutism, and seizures may develop, reflecting widespread cerebral and cerebellar involvement. The diagnosis of SCA17 relies on genetic testing to detect an abnormal CAA/CAG repeat expansion in TATA-binding protein (TBP), the only gene abnormality known to be associated with SCA17.

We describe two girls with atypical presentations of multisystem disorders due to deletions in mitochondrial DNA (mtDNA). One presented with painful carpopedal spasms due to hypoparathyroidism at the age of 4 years. The disease was rapidly progressive with development of truncal and limb ataxia, spastic paraparesis, muscle weakness and wasting, pigmentary retinal degeneration and sensorineural hearing loss. She had short stature and vitiligo patches, hirsutism, anaemia, diabetes mellitus and exocrine pancreatic dysfunction. The other girl presented at the age of 6 years with polydipsia, polyuria and fatigue due to renal tubular dysfunction. The disease was insidiously progressive with poor growth and development of sensorineural hearing loss, muscle weakness and truncal and limb ataxia. Morphological, enzyme histochemical and biochemical investigations indicated mitochondrial dysfunction of skeletal muscle, liver and kidney in one patient and of skeletal muscle and liver in the other. Both patients had large proportions of mtDNA molecules with deletion in liver, kidney, skeletal muscle and blood cells. It may be concluded that symptoms from several different organs may be the first manifestation of a mtDNA deletion disorder.

A 60-yr-old man developed progressive gait disturbance and limb ataxia at the age of 52. Family history was absent for neurological disorders. Examinations showed pure cerebellar syndrome. There was no retinal degeneration for 7 yr. A brain MRI done at the age of 56 showed atrophy of the cerebellar hemispheres and vermis. Genetic test confirmed the spinocerebellar ataxia type 7 with CAG repeat number of 42.

A 55-year-old man with a history of hypertension, hypercholesterolemia, and tobacco use presented with sudden onset bilateral deafness, gait ataxia, and dysarthria. Clinical examination disclosed left-sided limb ataxia, bilateral gaze-evoked nystagmus, dysarthria, and bilateral hearing loss. Brain MRI showed a bilateral anterior inferior cerebellar artery (AICA) infarction (figure, A). Fluorodeoxyglucose PET scan ([18F] FDG PET) performed because of mild frontal syndrome (euphoria and decreased spontaneous activity) showed a mild cerebellar and prefrontal cortex hypometabolism (figure, B). He recovered after 1 month without sequelae. Five months later, he complained of apathy, poor motivation, and lack of interest in previous hobbies. Neuropsychological investigations disclosed a mild impairment of processing speed, alphabetic verbal fluency, attention and executive dysfunction such as difficulties in planning and disturbed mental flexibility; semantic and episodic memory and praxis were normal. An [18F] FDG PET control showed a severe bilateral cerebellar, frontal, temporal, and parietal hypometabolism (figure, …

The spinocerebellar ataxias (SCAs) are a group of serious debilitating disorders characterized by gait and limb ataxia, disturbances of speech and oculomotor control, and other variable clinical features, usually with onset in adulthood (Harding 1983). Since the identification of the first gene is responsible for spinocerebellar ataxia type 1 (SCA1) (Orr et al. 1993), an increasing number of genes and chromosomal loci have been characterized, which demonstrates the wide genetic heterogeneity in these hereditary disorders (Schols et al. 2004; Taroni and Di Donato 2004; Duenas et al. 2006). To date, at least 28 different SCA subtypes have been described (SCA 1–8, 10–29) (Duenas et al. 2006; Dudding et al. 2004). SCA3/MJD mutations have a prevalence of 20–25% for all the SCA, with regional variations worldwide, (Silveira et al. 2002; Van de Warrenburg et al. 2002). The mutation incidence of SCA1, SCA2, SCA6 and SCA7, on average, displayed a prevalence of approximately 2–5% (Schols et al. 2004). However, the SCA1 mutations are most frequently identified in Africa (Bryer et al. 2003), while SCA2 mutations account for most of the cases in India, Cuba and Italy (Saleem et al. 2000; Brusco et al. 2004). The remaining SCA types are considered as rare mutations, identified in singular families or specific populations. In 2009, we ascertained a large SCA pedigree from northeastern China with a slowly progressive, isolated form of ataxia. In this paper, we describe our initial experience with genotyping, carrier testing, and prenatal diagnosis.

A 53-year-old man presented with episodes of orthostatic diplopia and gait and bilateral limb ataxia. Examination showed gait ataxia. MRI (figure) revealed bilateral watershed infarctions between medial and lateral branches of the …

Autosomal dominant cerebellar ataxia (ADCA) includes heterogeneous neurodegenerative diseases with or without various neurological signs and symptoms. Ishikawa et al reported a new type of ADCA, named chromosome16q22.1 linked ADCA (16q-ADCA), attributed to a heterozygous C→T substitution in the 5′ non-coding region of puratrophin-1 gene.1 We searched for this mutation in168 patients from 129 families with ADCA and found it in six patients. The patients generally showed late onset pure cerebellar ataxia similar to previous reports1,2 but two had mild axonal neuropathy and orthostatic hypotension (OH). Our results suggest that 16q-ADCA shows a broader clinical presentation than previously thought. ### Patient No 1 An 81-year-old Japanese woman had dysarthria at 52 years of age, unsteady gait at 56 years, limb ataxia at 76 years and severe truncal ataxia, requiring a wheelchair. Her family history included progressive ataxia in her older sister, younger brother and son. She had cervical spondylosis at the C3–C7 level. Ocular movement was almost normal. The score on the International Cooperating Ataxia Rating Scale3 (ICARS) was 66/100. Deep tendon reflexes (DTRs) were increased, with extensor plantar reflexes. Sensation of pain was almost normal, while vibratory sensation was moderately disturbed in the lower limbs. Passive head up tilt testing (HUT) performed at 60° for 30 min revealed OH, with …

Friedreich's ataxia (FRDA) is an autosomal recessive inherited disorder characterized by progressive gait and limb ataxia, dysarthria, areflexia, loss of vibratory and position sense, and a progressive motor weakness of central origin. Additional features include hypertrophic cardiomyopathy and diabetes. Large GAA repeat expansions in the first intron of the FXN gene are the most common mutation underlying FRDA. Patients show severely reduced levels of a FXN-encoded mitochondrial protein called frataxin. Frataxin deficiency is associated with abnormalities of iron metabolism: decreased iron-sulfur cluster (ISC) biogenesis, accumulation of iron in mitochondria and depletion in the cytosol, enhanced cellular iron uptake. Some models have also shown reduced heme synthesis. Evidence for oxidative stress has been reported. Respiratory chain dysfunction aggravates oxidative stress by increasing leakage of electrons and the formation of superoxide. In vitro studies have demonstrated that Frataxin deficient cells not only generate more free radicals, but also show a reduced capacity to mobilize antioxidant defenses. The search for experimental drugs increasing the amount of frataxin is a very active and timely area of investigation. In cellular and in animal model systems, the replacement of frataxin function seems to alleviate the symptoms or even completely reverse the phenotype. Therefore, drugs increasing the amount of frataxin are attractive candidates for novel therapies. This review will discuss recent findings on FRDA pathogenesis, frataxin function, new treatments, as well as recent animal and cellular models. Controversial aspects are also discussed.

Neurological manifestation of metronidazole toxicity include neuropathy and encephalopathy. We report a 67-year-old man with progressive painful paresthesias involving all the four limbs of 3 weeks' duration before admission. He had been treated with metronidazole and cephalosporin for 10 weeks for a hepatic abscess. Five weeks after the symptom onset, he complained of dysarthria and limb ataxia. Magnetic resonance imaging revealed signal abnormalities in the splenium of the corpus callosum and bilateral dentate nuclei. A few hours after brain imaging, the patient exhibited excessive diaphoresis and fluctuation in blood pressure, which resolved within several hours after discontinuation of metronidazole. Whereas his speech returned to near normal within approximately 1 week, a burning sensation was not completely relieved, even 6 months after discharge.

The spinocerebellar ataxias (SCA) are a large group of inherited disorders affecting the cerebellum and its afferent and efferent pathways. Their hallmark symptom is slowly progressive, symmetrical, midline, and appendicular ataxia. Some may also have associated hyperkinetic movements (chorea, dystonia, myoclonus, postural/action tremor, restless legs, rubral tremor, tics), which may aid in differential diagnosis and provide treatable targets to improve performance and quality of life in these progressive, incurable conditions. The typical dominant ataxias with associated hyperkinetic movements are SCA1–3, 6–8, 12, 14, 15, 17, 19–21, and 27. The common recessive ataxias with associated hyperkinetic movements are ataxia telangiectasia and Friedreich's ataxia. Fragile X tremor-ataxia syndrome (FXTAS) and multiple-system atrophy (a sporadic ataxia which is felt to have a genetic substrate) also have hyperkinetic features. A careful work-up should be done in all apparently sporadic cases, to rule out acquired causes of ataxia, some of which can cause hyperkinetic movements in addition to ataxia. Some testing should be done even in individuals with a confirmed genetic cause, as the presence of a secondary factor (nutritional deficiency, thyroid dysfunction) can contribute to the phenotype.

A 67-year-old woman presented with dysarthria and trunk and limb ataxia, which progressed in a subacute manner. Anti-glutamic acid decarboxylase antibodies were negative in the serum, but were detected in the cerebrospinal fluid. Steroid pulse therapy was administered on the suspicion that the presence of anti-glutamic acid decarboxylase antibodies in the cerebrospinal fluid might be associated with cerebellar ataxia. Treatment resulted in a marked improvement in clinical symptoms, leading to a diagnosis of anti-glutamic acid decarboxylase antibody-positive cerebellar ataxia. The outcome showed that measuring anti-glutamic acid decarboxylase antibodies levels in the cerebrospinal fluid is important, even when levels are negative in the serum.

A 55-year-old female was admitted to hospital after the acute onset of vertigo similar to thet of Meniere's disease. She also complained of nausea, vomiting, left tinnitus, left hearing loss and diplopia. A right Horner's syndrome, pain and temperature loss over the right side of the face and left trunk and limbs were noted. However, she had no limb ataxia or dysarthria. Magnetic resonance imaging (MRI) demonstrated a right inferior cerebellar infarction. Ocular motor abnormalities were : skew deviation, mixed horizontal-torsional nystagmus toward the left, and upbeating vertical nystagmus. In addition, in the positional nystagmus with the right-side (damaged side) down, vertical nystagmus was directed upward, and with the left-sidedown, anticlockwise torsional nystagmus of large amplitude appeared accompanied by an intense sensation of vertigo. We attribute the nystagmus to an imbalance of central projections from the anterior and posterior semicircular canals and the otolith receptors that mediate ocular counter-roll.

A 61-year-old man who experienced a sudden onset of unstable gait followed by nuchal pain was admitted to our department. The neurologic examination revealed right-sided limb ataxia, right partial ptosis, and decreased sensation to 50% of the normal side to pinprick and temperature stimuli on the left side below the level of the T-6 dermatome. A lateral medullary infarction caused by spontaneous vertebral artery dissection was diagnosed by magnetic resonance imaging and computed tomography angiography. In conclusion, lateral medullary infarction is an important entity to consider in the differential diagnosis of dermatomal sensory manifestations.

Spinocerebellar ataxias (SCAs) are dominantly inherited neurodegenerative disorders characterized by progressive cerebellar ataxia and dysarthria We have identified missense mutations in prodynorphin (PDYN) that cause SCA23 in four Dutch families displaying progressive gait and limb ataxia PDYN is the precursor protein for the opioid neuropeptides alpha neoendorphin, and dynorphins A and B (Dyn A and B) Dynorphins regulate pain processing and modulate the rewarding effects of addictive substances Three mutations were located in Dyn A a peptide with both opioid activities and nonoproid neurodegenerative actions Two of these mutations resulted in excessive generation of Dyn A in a cellular model system In addition two of the mutant Dyn A peptides induced toxicity above that of wild type Dyn A in cultured striatal neurons The fourth mutation was located in the nonoproid PDYN domain and was associated with altered expression of components of the oproid and glutamate system, as evident from analysis of SCA23 autopsy tissue Thus, alterations in Dyn A activities and/or impairment of secretory pathways by mutant PDYN may lead to glutamate neurotoxicity, which underlies Purkinje cell degeneration and ataxia PDYN mutations are identified in a small subset of ataxia families, indicating that SCA23 is an infrequent SCA type (similar to 0 5%) in the Netherlands and suggesting further genetic SCA heterogeneity

We have identified a novel form of recessive ataxia that segregates in three children of a large consanguineous Saudi Arabian family. The three patients presented with childhood onset gait and limb ataxia, dysarthria and had limited walking without aid into their teenage years. Two patients developed epilepsy at 7 months without relapse after treatment, and mental retardation. Linkage studies allowed us to identify a single locus that segregated with the disease on chromosome 3q28-qter. Mutation screening of all coding sequences revealed a single nucleotide deletion, 2927delC, in exon 19 of the KIAA0226 gene, which results in a frame shift of the C-terminal domain (p.Ala943ValfsX146). The KIAA0226 gene encodes a protein that we named rundataxin, with two conserved domains: an N-terminal RUN domain and a C-terminal domain containing a diacylglycerol binding-like motif. The closest paralogue of rundataxin, the plekstrin homology domain family member M1, has been shown to colocalize with Rab7, a small GTPase associated with late endosomes/lysosomes, suggesting that rundataxin may also be associated with vesicular trafficking and signalling pathways through its RUN and diacylglycerol binding-like domains. The rundataxin pathway appears therefore distinct from the ataxia pathways involving deficiency in mitochondrial or nuclear proteins and broadens the range of mechanisms leading to recessive ataxias.

Lesions in the cerebellum produce various symptoms related to balance and motor coordination. However, the relationship between the exact topographical localization of a lesion and the resulting symptoms is not well understood in humans. In this study, we analyzed 66 consecutive patients with isolated cerebellar infarctions demonstrated on diffusion-weighted magnetic resonance imaging. We identified the involved lobules in these patients using a cross-referencing tool of the picture archiving and communication system, and we investigated the relationships between the sites of the lesions and specific symptoms using χ (2) tests and logistic regression analysis. The most common symptoms in patients with isolated cerebellar infarctions were vertigo (87%) and lateropulsion (82%). Isolated vertigo or lateropulsion without any other symptoms was present in 38% of patients. On the other hand, limb ataxia was a presenting symptom in only 40% of the patients. Lateropulsion, vertigo, and nystagmus were more common in patients with a lesion in the caudal vermis. Logistic regression analysis showed that lesions in the posterior paravermis or nodulus were independently associated with lateropulsion. Lesions in the nodulus were associated with contralateral pulsion, and involvement of the culmen was associated with ipsilateral pulsion and isolated lateropulsion without vertigo. Nystagmus was associated with lesions in the pyramis lobule, while lesions of the anterior paravermis were associated with dysarthria and limb ataxia. Our results showed that the cerebellar lobules are responsible for producing specific symptoms in cerebellar stroke patients.

Ataxia is characterized clinically by four signs (gait and limb ataxia, dysarthria and nystagmus). Although ataxia has been described in posterior circulation (PC) stroke series, there are no prospective studies that have investigated a possible differential role of the cerebellum or its input/outputs in causing ataxia.Ataxia was semi-quantified according to the International Cooperative Ataxia Rating Scale (ICARS) in 92 consecutive patients with acute PC stroke. Four topographical patterns based on magnetic resonance imaging (MRI) findings were identified: picaCH pattern (posterior inferior cerebellar artery infarct); scaCH pattern (superior cerebellar artery infarct); CH/CP pattern (infarct involving both the cerebellum and the brainstem cerebellar pathways); and CP pattern (infarct involving the brainstem cerebellar pathways).Gait ataxia was present in 95.7%, limb ataxia in 76.1%, dysarthria in 56.5% and nystagmus in 65.2% of patients. Gait ataxia frequency did not differ between the patterns, but was significantly more severe in the CH/CP pattern than in either picaCH (P=0.0059) or CP (P=0.0065) pattern. Limb ataxia was significantly less frequent (P0.001) and less severe (P0.001) in picaCH pattern than other patterns. Dysarthria was less frequent in picaCH pattern than in other patterns (P=0.018) and less severe than in scaCH (P=0.0043) or CP (P=0.0047) pattern. No differences in nystagmus frequency or severity were observed across all four patterns.In PC stroke gait ataxia was almost always present, regardless of the lesion site. Limb ataxia and dysarthria were less frequent in the picaCH pattern, whereas nystagmus, when present, did not differ among the topographical patterns.

We report the case of a 40-year-old right-handed German-speaking man who presented with ischemic stroke in the territories of the right superior cerebellar artery and posterior inferior cerebellar artery. The objective of the present study was to investigate the consequences of this cerebellar damage with regard to higher cognitive functions. On admission to the stroke unit, the patient presented with dysarthria, right-sided appendicular ataxia, gait ataxia, and right-sided horizontal nystagmus (National Institutes of Health Stroke Scale, NIHSS, score 4). When examined 10 days after his stroke using a set of neuropsychological tests, he showed a marked deficit in the ability to remember when and in which context he had previously encountered verbal material. This aspect of memory, so-called ‘source memory’, is known to be mediated mainly by frontal and medial temporal structures. The present case suggests the existence of a strong functional connectivity between cerebellum and cortical regions underlying specific memory processes.

Oculomotor palsies are known to cause past pointing in reaching for visual targets. Disturbances of gait may also occur, but have not been reported extensively. The authors present two patients with an oculomotor palsy, one of central and the other of peripheral origin, who complained of unsteady gait. When using their affected eye, they showed gait deviations characterized by veering in the direction of action of the paralyzed medial rectus. The ataxia was present only when they were looking monocularly with the affected eye and disappeared when the intact eye was used. The authors suggest that the gait ataxia was caused by a ‘past-stepping’ analogous to the past-pointing of the upper extremity.

Friedreich ataxia is the most frequent hereditary ataxia, with an estimated prevalence of 3-4 cases per 100,000 individuals. This autosomal-recessive neurodegenerative disease is characterized by progressive gait and limb ataxia, dysarthria, lower-limb areflexia, decreased vibration sense, muscular weakness in the legs, and a positive extensor plantar response. Non-neurological signs include hypertrophic cardiomyopathy and diabetes mellitus. Symptom onset typically occurs around puberty, and life expectancy is 40-50 years. Friedreich ataxia is usually caused by a large GAA-triplet-repeat expansion within the first intron of the frataxin (FXN) gene. FXN mutations cause deficiencies of the iron-sulfur cluster-containing subunits of the mitochondrial electron transport complexes I, II, and III, and of the iron-sulfur protein aconitase. Mitochondrial dysfunction has been addressed in several open-label, non-placebo-controlled trials, which indicated that treatment with idebenone might ameliorate hypertrophic cardiomyopathy; a well-designed phase II trial suggested concentration-dependent functional improvements in non-wheelchair-bound children and adolescents. Other current experimental approaches address iron-mediated toxicity, or aim to increase FXN expression through the use of erythropoietin and histone deacetylase inhibitors. This Review provides guidelines, from a European perspective, for the diagnosis of Friedreich ataxia, differential diagnosis of ataxias and genetic counseling, and treatment of neurological and non-neurological symptoms.

We report on a 28-year-old man with a 2-year history of Vogt-Koyanagi-Harada disease (VKH), who developed one-and-a-half syndrome, facial hypoesthesia, facial nerve palsy, hearing loss and limb ataxia on the right side. An MRI showed inflammatory lesions in the pons extending into the left middle cerebellar peduncle. Corticosteroid treatment successfully ameliorated his symptoms and lesions. This patient demonstrated the possible association of brainstem encephalitis with VKH.

Internuclear ophthalmoplegia (INO) is a complex ocular motility disorder caused by damage to the medial longitudinal fasciculus. The occurrence of hemi-seesaw nystagmus in an INO patient has been reported rarely. This nystagmus may be caused by damage to the pathway from the contralateral vertical semicircular canal. The ocular tilt reaction is characterized by ipsilateral head and neck tilt, skew deviation, and ocular torsion. We report a patient who presented with hemi-seesaw nystagmus, ocular tilt reaction, and limb ataxia combined with an INO from a right focal pontine infarction. INO may be accompanied by a variety of ocular findings associated with the disruption of the medial longitudinal fasciculus.

Friedreich Ataxia (FRDA), the most frequent inherited ataxia, is not only characterized by progressive gait and limb ataxia, but in most cases is also accompanied by a severe hypertrophic cardiomyopathy. This life threatening symptom can be ameliorated by the administration of idebenone, a short chain quinone antioxidant, supporting additional evidence that oxidative stress plays a major role in the pathogenesis of this disease. In this study we analyze the combinatorial effect of different antioxidants on cell viability of FRDA fibroblasts and of RAT-1 immortalized fibroblasts exposed to oxidative stress. We find that an equimolar mixture of idebenone and vitamin E is more potent than each of the compound alone. Increased potency was also obtained with a novel synthetic antioxidant (Fe-Aox29) combining the active groups from both idebenone and vitamin E. These results indicate, that idebenone and vitamin E might act synergistically to counteract oxidative stress in fibroblasts from FRDA patients.

Publisher Summary A variety of metabolic insults can result in cerebellar dysfunction and ataxia. This chapter discusses diseases that are related to the defects of mitochondrial function and various metabolic pathways. It discusses chronic progressive external ophthalmoplegia (CPEO) and Kearns–Sayre syndrome (KSS), encephalomyopathies, neurogenic weakness ataxia and retinal pigmentation (narp), Leigh syndrome (LS), Friedreich's ataxia (FRDA), twinkle mutations, and polymerase gamma mutations. CPEO is predominantly a myopathic disorder, but there have been reports of dementia, seizures, myoclonus, and stroke-like episodes. In a study of 66 patients, there was mild limb or gait ataxia in 41%. The common mitochondrial encephalopathies include myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and myoclonic epilepsy and ragged red fibers (RRFs) (MERRF). MELAS can include psychomotor retardation, ataxia, cognitive impairment, deafness, diabetes mellitus, and limb weakness. NARP are peripheral neuropathy, ataxia, retinitis pigmentosa, seizures, and dementia. LS is a subacute necrotizing encephalomyelopathy characterized by bilateral symmetric focal necrotic lesions within the thalamus and extending into the pons, inferior olives, and spinal cord. FRDA is an autosomal recessive disease characterized clinically by a progressive gait and limb ataxia, absence of deep tendon reflexes, and the loss of position and vibration sense in the lower limbs.

Background: Limb ataxia is classically attributed to cerebellar hemispheric lesions, although isolated lesions of the inferior cerebellar peduncle (ICP) in the medulla may also cause this sign. It is still unclear why only some patients with acute cerebellar infarcts in the posterior inferior cerebellar artery (PICA) territory present with limb ataxia. The proximal intracranial posterior circulation (P-PC) territory includes structures fed by the intracranial vertebral arteries (ICVAs): the medulla, supplied by small ICVAs branches, and posterior inferior portion of the cerebellum, fed by PICA. ICP and PICA territory cerebellar infarcts most often occur independently but occasionally occur together. Objective: To identify structures responsible for limb ataxia in acute P-PC brain infarcts correlating clinical and topographical findings. Methods: Sixteen patients (8 women) were included with ages ranging from 30 to 82 years (mean age, 62 years) with isolated acute strokes in the P-PC territory. Results: The cases reported here indicate that limb ataxia in acute P-PC territory infarcts may be associated with a damage to the ICP in the dorsolateral medulla, regardless of a hemispheric cerebellar lesion. In fact among the 9 patients with PICA stroke, limb ataxia was observed only in the 2 patients who also presented a damage to the dorsolateral medulla involving the ICP. Of the 7 patients with isolated dorsolateral medullary infarct, only 5 patients with an ICP damage had limb ataxia. Conclusions: When correlating limb ataxia and acute P-PC infarcts it is important to take in account the entire ICVA territory.

A 29-year-old Hmong woman presented with 3 months of worsening imbalance and intermittent vertigo followed by right facial numbness, slurred/nonsensical speech, and memory impairment. She reported generalized weakness, fatigue, and anorexia with more than 10 kg weight loss. She denied paresthesia, vision loss, nausea, vomiting, or hiccups. Neurologic examination revealed impaired short-term memory, expressive aphasia, mild right appendicular ataxia, and profound abulia.

We have studied a man with an atypical form of Friedreich's ataxia (FRDA), who presented at age 26 years with a 2-year history of unsteadiness and clumsiness. The predominant feature of his initial neurological examination was a spastic paraparesis, along with a mild distal weakness and hyperreflexia of the upper limbs. He also displayed limb ataxia. Frataxin GAA repeat sizes were 1,040/690. This unusual FRDA presentation is not dissimilar to that of Acadian spastic ataxia.

We report here a case of 18 year old male with tremors of hands, deafness, tendency to fall while walking, drowsiness and double vision of total duration 1(1/2) years. He had internuclear ophthalmoplegia, broken saccades, hypertonia and hyperreflexia of all four limbs, intention tremors, signs of gait and limb ataxia. Pupillary reactions and fundus examination were normal and signs of meningeal irritation or sensory neurological deficit were absent. MRI head and cervical spine with gadolinium enhancement revealed demyelination as evident from multiple oblong foci isointense on T1-weighted images and hyperintense on T2-weighted and fluid attenuated inversion recovery sequences in corpus callosum, sub-cortical white matter, right thalamus, pons and periaqueductal region of midbrain. Ill-defined linear hyperintense signals were observed in cervical spinal cord. No skeletal abnormality was noted in the skull or cervical spine. Oligoclonal bands were present in the cerebrospinal fluid. Brainstem auditory evoked potentials were abnormal, although visual evoked potentials were in normal range. A diagnosis of primary progressive multiple sclerosis (PPMS) was made fulfilling the revised criteria as laid down. In view of its presentation, it is a unique case of PPMS from India.

High levels of antibodies to the 65-kd isoform of glutamic acid decarboxylase (GAD65) are observed in some cases of sporadic, progressive cerebellar ataxia and suggest a potential autoimmune etiology.1-3 Few studies have examined immunotherapy in GAD65-associated ataxia.1,4 We describe a patient with GAD65 ataxia who responded to IV methylprednisolone (IVMP) but not to plasma exchange. Oral azathioprine has provided a sustained clinical remission. A 70-year-old man with type 2 diabetes mellitus and unremarkable family history presented with 9 months of progressive ataxia, beginning with left hemiataxia and dysarthria. He later developed right hemiataxia, progressive gait instability, dysmetria, spasticity, worsening dysarthria, and dysphagia with 5- to 10-kg weight loss. On exam he had loud, scanning, dysarthric speech, gaze-evoked nystagmus, saccadic intrusions, dysmetric saccades, spastic tone and bilateral Babinski signs, marked left greater than right limb ataxia with gross action tremor, dysmetria, and dysdiadokinesia (video). He was unable to stand or walk because of ataxia and received a gastrostomy tube for dysphagia and aspiration. His score on the International Cooperative Ataxia Rating Scale (ICARS) was 78 of …

1. Clinical backgroundA 58-year-old man presented with a four-year history ofgradually increasing gait unsteadiness, urinary inconti-nence and erectile dysfunction. His daughter complainedthat he snored loudly at night, but on further questioningit was apparent that this was an inspiratory stridor. Therewas no other past history, and no family history of note.Examination showed gaze-evoked nystagmus, mild dysar-thria, and severe truncal and limb ataxia. Blood pressuredid not fall on standing. An MRI brain was performed(Figs. 1, 2).2. What is the most likely diagnosis?1. Idiopathic late onset cerebellar ataxia.2. Olivo-ponto-cerebellar atrophy variant of multiple sys-tem atrophy.3. Spino-cerebellar ataxia.4. Gluten ataxia.Answer on page 307.

Cockayne syndrome is a multi‐systemic, autosomal recessive disease characterised by postnatal growth failure and progressive multi‐organ dysfunction. The main clinical features are severe dwarfism (

The authors studied 14 patients with an isolated cerebellar infarct in the territory of the medial branch of the superior cerebellar artery (MSCA). The most common clinical finding was severe gait ataxia with sudden falling (n = 9) or severe veering (n = 2). Cerebellar dysarthria was found in 8 patients. Eight patients had a mild unilateral limb ataxia. These findings emphasize that MSCA territory cerebellar infarction presented with the prominent gait ataxia and cerebellar dysarthria.

Publisher Summary The Wallenberg syndrome or dorso-lateral medullary infarction is the most common vascular syndrome of the medulla oblongata. Its clinical features include an ipsilateral Horner's syndrome, an ipsilateral limb ataxia, and mostly an ipsilateral but sometimes also a contralateral or bilateral decrease of pain and temperature sensibility of the face. Patients with Wallenberg's syndrome and with morphological (lesion) or functional (ipsilateral sensory deficit and delayed late blink reflex responses) show evidence of damage to the trigeminal tract and nucleus with sparing of the nucleus caudalis would develop facial pain. The trigeminal trophic syndrome (TTS), a very rare complication of Wallenberg's syndrome, can occur with and without central poststroke pain (CPSP). In these patients, itch is the predominant complaint causing facial ulcerations maintained by picking and scratching. Ongoing itch is a matter of not only neural injury but also missing inhibition. The intensity and duration of scratching provoked by itch are reduced with the onset of pain. The lack of pain sensibility in most patients with itch following TTS may result in this kind of missing inhibition. TTS patients often, but not always, suffer from diseases leading to a reduction of central inhibitory mechanisms, such as dementia or bipolar depression.

The aim of the present study was to examine somatotopy in the cerebellar cortex and a possible differential role of the cerebellar cortex and nuclei in functional outcome. Clinical findings and 3D MRI-based cerebellar lesions site were compared in a group of 90 patients with focal cerebellar lesion using International Cooperative Ataxia Rating Scale (ICARS) and voxel-based lesion–symptom mapping (VLSM). Separate analysis was performed in patients with acute and chronic ischemic lesions (n = 43) and patients with acute and chronic surgical lesions (n = 47). Thirty-eight patients were included after resection of a cerebellar tumor in childhood or adolescence. The most significant lesion symptom correlations were observed in the subgroup with acute ischemic lesions. Limb ataxia was significantly correlated with lesions of the interposed (NI) and part of the dentate nuclei (ND), ataxia of posture and gait with lesions of the fastigial nuclei (NF) including NI. Correlations with cortical lesions were less significant and present in the superior cerebellum only. Upper limb ataxia was correlated with lesions of vermal, paravermal and hemispheral lobules IV–V and VI, lower limb ataxia with lesions of vermal, paravermal and hemispheral lobules III and VI, dysarthria with lesions of paravermal and hemispheral lobules V and VI and ataxia of posture and gait with lesions of vermal and paravermal lobules II, III and IV. In the subgroups with chronic focal lesions, similar correlations were observed with lesions of the cerebellar nuclei, but significantly less correlations with lesions of the cerebellar cortex. Functional localization based on VLSM backs findings in previous animal and functional brain images studies in healthy human subjects. The lesion site appears to be critical for motor recovery. Lesions affecting the cerebellar nuclei are not fully compensated at any age and independent of the pathology in humans.

This female patient was born to healthy parents who were first cousins. Her elder brother and two paternal uncles had a disorder similar to hers. She began to walk at the age of 1 years and 6 months. During childhood, she was physically small and mentally retarded. To receive special education, she went to school on foot. Gait ataxia appeared at the age of 19 years, and gradually worsened thereafter. When she was 31 years of age, she became unable to walk unsupported. She showed progressive loss of vision and hearing, spoke fewer words than previously, and complained of fear and insomnia. At the age of 32 years, she was institutionalized at a facility for the severely handicapped. On admission, she showed dwarfism (113 cm in height), emaciation (18 kg in weight) and pigmentation of the skin. Her head was small and her face showed a senile-like appearance with sunken eyes, cataract and malpositioned teeth. Neurological examination disclosed severe impairment of hearing and vision, dysarthria, muscle hypertonia, truncal and limb ataxia, spontaneous extension of the toes, and emotional instability. Her mental age was between 1 and 3 years. Laboratory examination showed hyperuricemia and slow conduction velocity of the peripheral nerves. Ultrasonography of the abdomen demonstrated thinning of the renal cortex. Computed tomography of her head showed diffuse cerebral atrophy, ventriculomegaly, and symmetrical calcification of the basal ganglia and cerebellar medulla (Fig. 1). On magnetic resonance imaging, the calcified lesions showed T1and T2-shortening. The cerebral white matter was atrophic and showed patchy T1and T2elongation (Fig. 1). At the age of 34 years, restlessness and anxiety worsened. She refused to eat, had epileptic attacks, and underwent hydration and medication with neuroleptic, hypnotic and antiepileptic drugs. Several months later, she became somnolent and developed fever, vomiting and hypertension, followed by coma, muscle rigidity and abnormal respiration. A high serum level of creatine kinase suggested a diagnosis of neuroleptic malignant syndrome. After approximately a week, she died at the age of 35 years.

Body lateropulsion may occur without signs of vestibular dysfunction and vestibular nucleus involvement. The authors examined 10 such patients with three-dimensional brainstem mapping. Body lateropulsion without limb ataxia reflected an impairment of vestibulospinal postural control caused by a lesion of the descending lateral vestibulospinal tract, whereas body lateropulsion with limb ataxia was probably the consequence of impaired or absent proprioceptive information caused by a lesion of the ascending dorsal spino-cerebellar tract.