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Cladribine; Disease-modifying drugs; Relapsing multiple sclerosis Cladribina; Medicaments modificadors de malalties; Esclerosi múltiple recurrent Cladribina; Medicamentos modificadores de enfermedades; Esclerosis múltiple recurrente Cladribine is a disease-modifying selective immune reconstitution oral therapy for adult patients with highly active relapsing multiple sclerosis (RMS). It was approved in the USA in 2019 and in Europe in 2017, thus there are still gaps in existing guidelines for using cladribine tablets in clinical practice. Nine experts with extensive experience in managing patients with multiple sclerosis in Spain identified some of the unanswered questions related to the real-life use of cladribine tablets. They reviewed the available clinical trial data and real-world evidence, including their own experiences of using cladribine, over the course of three virtual meetings held between November 2020 and January 2021. This article gathers their practical recommendations to aid treatment decision-making and optimise the use of cladribine tablets in patients with RMS. The consensus recommendations cover the following areas: candidate patient profiles, switching strategies (to and from cladribine), managing response to cladribine and safety considerations. The publication of this article, as well as journal’s Rapid Service Fee, was funded by Merck, S.L.U., Mollet del Valles, Spain, an affiliate of Merck KGaA.

The spinocerebellar ataxia recessive type 10 is a genetic form associated with ANO10 gene mutations. Affected individuals present with ataxia, hyperreflexia, ocular movement disorders and cerebellar atrophy. The homozygous variant in the ANO10 gene NP_060545.3:p.Asn114* is a 2-nucleotide deletion that would cause the introduction of a premature stop codon at the same position, that has not been previously described in the scientific literature related to disease and it perfectly explains our patient’s condition.

Background: The increase in available disease modifying therapies (DMTs) for multiple sclerosis has led to greater emphasis on improving treatment sequencing paradigms. This article summarises the opinions from a panel of 25 experts on treatment switching approaches in relapsing multiple sclerosis (RMS).Methods: A modified Delphi consensus process was carried out to develop clinically relevant statements for aiding treatment decisions in patients with RMS between the 16th January and the 9th October 2019. A sub-group of two experts (core group) carried out an extensive review of the literature and formulated 106 statements for the expert panel to evaluate.Results: From a total number of 106 statements that were submitted to the expert panel for critical evaluation, consensus (at least 80% of the panelists agreed) was reached on 99 of them. These statements cover treatment objectives, reasons for DMT switching, suboptimal response criteria, strategies for treatment change and washout periods.Conclusion: The agreed statements provide up-to-date guidance on DMT sequencing for optimal patient management.

Isolated cranial nerve involvement in multiple sclerosis (MS) patients is not frequent. Deafness is considered to be uncommon in MS patients. We have reviewed the sensorineural hearing loss episodes that had been thoroughly investigated in our hospital in the last 5 years. We present three cases of sensorineural hearing loss in patients with MS and compare them with other previously reported and discuss this uncommon symptom. The cases that we present were firstly evaluated by an otolaryngologist. A lesion is seen at the root-entry zone of the eighth cranial nerve in only one case, but no lesions are seen in the other cases. A retrocochlear demyelinating disorder was demonstrated in the two patients in whom brainstem auditory evoked potentials were performed. All patients recovered at least partially their hearing functions.

Las enfermedades neurologicas suponen una causa importante de morbilidad en los paises desarrollados y, con frecuencia, conllevan alteraciones en el nivel de conciencia o en los mecanismos de la deglucion que pueden hacer necesario un soporte nutricional artificial. La presente revision tratara de evaluar, basandose en la mejor evidencia cientifica disponible, el soporte nutricional en la enfermedad cerebrovascular aguda, la demencia y la esclerosis lateral amiotrofica, asi como la utilidad de la dieta cetogenica en el tratamiento de la epilepsia. Se realizo una busqueda bibliografica en MEDLINE (PubMed) y en la Cochrane Library Plus en espanol, y se seleccionaron estudios clinicos aleatorizados, revisiones sistematicas y metaanalisis. Existen escasos ensayos prospectivos aleatorizados sobre soporte nutricional en enfermedades neurologicas. El estudio FOOD muestra que la sonda nasogastrica es mejor via que la gastrostomia endoscopica percutanea para la nutricion enteral en el primer mes tras un ictus. En el caso de la demencia y otras enfermedades neurodegenerativas, las evidencias disponibles son debiles. No hay pruebas fiables procedentes de ensayos controlados aleatorizados que apoyen el uso de dietas cetogenicas en los pacientes con epilepsia.

Los micronutrientes, vitaminas y minerales, son compuestos necesarios para mantener un estado fisiologico adecuado. Su carencia ocasiona un sindrome complejo de sintomas y signos, bien caracterizado para cada vitamina y mineral, y que evoluciona en 3 etapas: deplecion de las reservas, disfuncion bioquimica y, finalmente, estado carencial, que puede manifestarse en cualquier organo o sistema. En la actualidad, las enfermedades carenciales solo se dan, en el caso de los paises occidentales, en ciertos grupos de riesgo, pero aun siguen siendo un problema sanitario importante en paises subdesarrollados. El diagnostico de las carencias nutricionales comienza con la identificacion de situaciones de riesgo nutricional. La anamnesis y una exploracion fisica cuidadosa del paciente son clave en su deteccion.

As Parkinson's disease progresses, its non-motor manifestations become increasingly more apparent to the point where, in advances phases of the disease, they are the most important clinical symptoms. A very wide range of non-motor symptoms can appear in Parkinson's disease. Impairment of the urinary function and the sexual function (understood as the capacity to carry out sexual activity) can be seen as belonging to the dysautonomic disorders. Hypersexuality would be included within the group of impulse control disorders.This study reviews the epidemiology, phenomenology and treatment of urinary disorders, sexual dysfunction and hypersexuality as non-motor symptoms of Parkinson's disease.Urinary disorders are the most frequent non-motor symptom in Parkinson's disease. They usually present as nocturia, urgency and increased mictional frequency (pollakiuria). Preferred treatment is with anticholinergic agents. Sexual dysfunction is a frequent complaint in patients with Parkinson. It has a multifactorial aetiology and is more frequent in males than in females. In males it manifests mainly as incapacity to achieve an erection, premature ejaculation or loss of the capacity to ejaculate, whereas in females the predominant signs are decreased libido, lowered arousal and difficulty in reaching an orgasm. Hypersexuality affects young males above all and has been related to the use of dopamine agonists.

Chorea is a brief, random, involuntary movement that can affect any muscle group and flows in an unpredictable manner from one part of the body to another. Choreic movements are present at rest, increase with distracting manoeuvres, can be partially suppressed and often disappear during sleep. The differential diagnosis of choreic syndromes is very wide and includes both genetic and acquired causes (cerebrovascular disease and space-occupying lesions, immune-based choreas, choreas caused by infection, toxic and metabolic encephalopathies, and choreas induced by pharmaceuticals).We review the phenomenology and pathophysiology of choreic movements, the most frequent causes, the diagnostic process and the most important recent findings in its treatment.Huntington's disease is the most frequent cause of hereditary chorea. In patients with a familial picture suggesting Huntington's disease, but with a negative genetic study, the chances of reaching a definitive diagnosis are, today, very low. Medication is the most frequent cause of acquired chorea. When dealing with a case of hemichorea, it is essential to rule out structural insult of the basal ganglia or their connections. Treatment of choreas must be aimed at correcting their cause if it is reversible, although the patient must always be given symptomatic treatment if the intensity and functional repercussions of the chorea require it. In cases of hereditary choreas, prevention could involve genetic counselling aimed at affected patients and their relatives.

Sirs: Paraneoplastic neurological syndromes (PNS) are disorders that occur in patients with systemic cancer, which are not due to direct tumour invasion or metastasis, chemotherapy or radiotherapy-induced neurotoxicity, coagulopathy, infection or metabolic or nutritional deficits. They are mediated by immunological mechanisms related to onconeural antigens expression by cancer cells [1]. Paraneoplastic optic neuropathy is an uncommon disorder [2–8]. We describe a patient with an isolated optic neuropathy associated with small-cell lung cancer and anti-CV2 antibodies. The patient was a 64-year-old heavy-smoker male who developed painless, progressive vision loss in his left eye, with only perception of movement 5 days after onset and mild visual loss in his right eye 2 days later. General and neurological examination revealed no abnormalities. Visual acuity was 0.4 in the right eye and only movement perception in the left one; a left relative afferent pupillary defect was present. Funduscopy showed right eye papilledema, whereas the left papilla was pale. Fluorescein angiography showed vitreous turbidity and dye enhancement in both papillae; no signs of retinitis or vasculitis were found. Blood analysis, including ESR, thyroid function tests, angiotensin-converting enzyme levels, autoantibodies and tumour markers (including neuron-specific enolase), were negative. CSF showed five mononuclear cells/ mm, a protein level of 78 mg/dl and no oligoclonal bands. Cytological examination was negative. Anti-CV2 antibodies were found in serum (1/8,000) and CSF (1/400), but not in aqueous humour. Brain MRI showed no abnormalities. Visual evoked potentials showed reduced amplitudes and mildly prolonged P100 latencies. Electroretinography was normal. A thorax CT scan revealed a 3-cm cystic nodule in the right superior lobe. Video-assisted thoracoscopy with lung biopsy was done; smallcell lung cancer was diagnosed. Methylprednisolone (1 g iv. daily for 5 days) was given and chemotherapy (cisplatin plus etoposide) was started after diagnosis of limited-stage disease. Fifteen months after diagnosis visual acuity was 0.7 in both eyes and no further relapses nor new neurological symptoms or signs developed over follow-up. Anti-CV2 antibodies remained in the serum sample at the same titer of 1/8,000. We report a patient with a seven-day history of painless, progressive, asymmetric, optic neuropathy as the only manifestation of small-cell lung cancer associated with anti-CV2 antibodies. Anti-CV2 (also called CRMP5-IgG) is an IgG autoantibody specific for the 62 kDa collapsing response-mediator protein 5 (CRMP-5) [9, 10]. Both the retina and the optic nerve contain full-length CRMP-5 protein. AntiCV2/CRMP-5 antibodies are markers of paraneoplastic autoimmunity related to lung cancer (mainly small-cell type) or thymoma [9, 10]. Graus et al. [11] have recently recommended diagnostic criteria for PNS. Although optic neuropathy is not a classical syndrome, our patient fulfills criteria for PNS as a non-classical syndrome with onconeural antibodies (anti-CV2/CRMP-5) and cancer (small-cell carcinoma). Response to therapy (steroids and chemotherapy) can be interpreted as an additional data supporting the diagnosis. Optic neuropathy is an uncommon paraneoplastic manifestation of cancer. Up to date, only 42 patients with paraneoplastic optic neuropathy have been reported in the English literature. However, nearly always patients had other neurological symptoms or signs, such as neuropathy, cerebellar ataxia, dementia, other cranial nerve abnormalities, A. Ares-Luque (&) L.A. Garcia-Tunon AE B.C. Cabezas L.E. Hernandez-Echebarria AE J. Tejada Neurology Dept. Hospital de Leon C/ Altos de Nava sn. 24071 Leon, Spain Tel.: +34-98/7237400 Fax: +34-98/7240503 E-Mail: adrianares@telefonica.net

WCN 2013 No: 2470 Topic: 2 — Movement Disorders Central extrapontine myelinolysis appearing as acute parkinsonism R. Garcia Santiago, L. Redondo Robles, M.C. Riveira Rodriguez, S. Fernandez Menendez, A. Ares Luque, A. Galiana Ivars, N. Gonzalez Nafria, J. Tejada, B. Cabezas Delamare. Hospital of Leon, Leon, Spain Background: When facing an acute parkinsonism, we must take into account not only the secondary and most frequent etiologies, such as the pharmacological, vascular or toxicological ones, but also others which are less common. Case report: We present the case of a 29-year-old man, who is admitted in our Neurology department with high frequency, constant and incapacitating rest and postural tremor, which was present for 5 days prior to the admission. It was accompanied by rigidity and bradykinesia – all of it with predominance in the right side of the body – as well as hypomimia, dysprosody and abundant sialorrhea. Postural reflexes were also seriously damaged. As a precedent, he had beenhospitalised thatmonthwith an addisonian crisis, and his sodium levels had increased from 109 to 138 mEq/L in a day. MRI evidenced a bilateral hyperintensity of the basal ganglia, which is compatible with central extrapontine myelinolysis. The DaTSCAN was normal. Conclusion: We would like to express the importance of treating hyponatremia in a slow way, because of the risks of osmotic demyelination of the central nervous system, not only distinctly at the pontine level, but also in other locations. Additionally, we would also like to emphasize the importance of the careful analysis of the patient's history, searching for processes with a possible damage of the basal ganglia. Thus, we will be able to find the diagnosis of more infrequent etiologies of parkinsonism, as was the case here. doi:10.1016/j.jns.2013.07.556 Abstract — WCN 2013 No: 2476 Topic: 2 — Movement Disorders Impulse control disorder in psychogenic parkinsonism WCN 2013 No: 2476 Topic: 2 — Movement Disorders Impulse control disorder in psychogenic parkinsonism S. Budrewicz, K. Slotwinski, M. Koszewicz, A. Dolgan, R. Podemski. Neurology, Wroclaw Medical University, Wroclaw, Poland Psychogenic movement disorders (PMD) appear in 1.9% of general population and in 2.25% patients with neurological diseases. Psychogenic parkinsonism (PP) is rare and accounts for less than 10% of PMD. The psychogenic parkinsonism is estimated of 0.17% of all cases of parkinsonism. The authors present the case of 53-year old woman with long-standing recognition of Parkinson disease (PD) with motor fluctuations and dyskinesias, treated with L-Dopa, ropinirol and amantadine. She was admitted to theNeurological Department ofWroclawMedical University in order to confirm the PD diagnosis, estimate the appropriate treatment or eventually qualify to the operation. The medical history indicated to the impulse control disorders (ICD)— compulsion for the internet usage, shopping (she bought the same, useless things repeatedly). The analysis of the medical history, observation of the motor symptoms and their changes, nonspecific influence of dopaminergic treatment, psychological and psychiatric evaluations allowed us to recognize psychogenic parkinsonism (the Jankovic criteria 1, 2, 6, 7, 8) for the certain recognition of PP. Despite of any changes of the dopaminergic treatment, the compulsive actions disappeared spontaneously. Slow discontinuation of the dopaminergic treatment did not enhance the typical for PD motor disturbances. The influence of dopaminergic agonists and L-Dopa treatment aswell as familiar, psychiatric disorder (patient's mother suffered from bipolar disorder) or conversion with taking the pattern from the internet, was thought to be important in the etiology of ICD in our patient. doi:10.1016/j.jns.2013.07.557 Abstract — WCN 2013 No: 2274 Topic: 2 — Movement Disorders Novel mutations in cathepsin D in juvenile onset neuronal ceroid lipofuscinosis WCN 2013 No: 2274 Topic: 2 — Movement Disorders Novel mutations in cathepsin D in juvenile onset neuronal ceroid lipofuscinosis J. Hersheson, D. Burke, H. Houlden. Molecular Neuroscience, Institute of Neurology, UK; Department of Chemical Pathology, Great Ormond Street Hospital for Children NHS Trust, London, UK Background: Mutations in cathepsin D (CTSD) have been previously reported in patients with neuronal ceroid lipofuscinosis (CLN10). To date only 7 mutations have been reported in four families with an NCL-like illness. We report the identification of two novel homozygous mutations in two families with juvenile onset ataxia and retinitis pigmentosa. Methods: Exome sequencing combined with homozygosity mapping was employed to identify a novel CTSD mutation in a single patient. This patient presented age 14 years with retinitis, progressive ataxia and cognitive impairment and had previously been screened for the known lysosomal storage disorders. The coding exons of CTSD were subsequently screened in 95 patients with complex ataxia and retinitis pigmentosa. One additional patient was identified with a further novel CTSD mutation. catD activity was then assayed in patient fibroblasts and leucocytes using a fluorometric assay. Results: 2 novel homozygous mutations were identified in exons 4 and 9 in the respective patients. Both presented with a juvenile onset of retinitis pigmentosa, ataxia and cognitive impairment. Fluorometric assay of the catD function revealed significantly reduced activity compared to controls in both individuals. The assay was also optimised for use in homogenised leucocyte pellets in addition to fibroblast samples. Discussion: This study reports two novel mutations that have been demonstrated to result in significant reduction in catD activity. This study expands range of mutations in CLN10 and also provides further insight into the range of phenotypes associated with the disorder. Patients with complex ataxia and retinitis should be screened for CTSD deficiency. doi:10.1016/j.jns.2013.07.558 Abstract — WCN 2013 No: 2465 Topic: 2 — Movement Disorders Self-assessment of dysarthria in Parkinson's disease verified by use of computer acoustic speech analysis WCN 2013 No: 2465 Topic: 2 — Movement Disorders Self-assessment of dysarthria in Parkinson's disease verified by use of computer acoustic speech analysis S. Budrewicz, M. Koszewicz, K. Slotwinski, R. Podemski. Neurology, Wroclaw Medical University, Wroclaw, Poland Abstracts / Journal of the Neurological Sciences 333 (2013) e65–e108 e81

Introduccion. Una emergencia en trastornos del movimiento es cualquier trastorno neurologico, de instauracion aguda o subaguda, en el cual la principal manifestacion clinica es un trastorno del movimiento primario, que persiste durante horas o dias, y en el que cualquier fallo en el diagnostico preciso o en el manejo del paciente puede dar lugar a una importante morbilidad o incluso mortalidad. Aunque son muy infrecuentes, es importante reconocer estos cuadros clinicos porque la gravedad de los sintomas y signos lleva a los pacientes a solicitar atencion medica urgente. Desarrollo. Diferenciamos dos escenarios diferentes: el debut abrupto de un trastorno del movimiento o la exacerbacion de un trastorno del movimiento ya existente. Es esencial realizar un diagnostico sindromico y etiologico precoces para poder llevar a cabo un manejo urgente adecuado. El espectro de causas posibles es muy amplio, pero es esencial recordar que la etiologia farmacologica es muy frecuente y comun a todas ellas. Conclusiones. La actitud general a seguir en un paciente que acude a urgencias por un trastorno del movimiento es indagar sobre el consumo de farmacos o drogas, preguntar sobre enfermedades neurologicas y psiquiatricas previas e intentar categorizar el trastorno del movimiento entre las diferentes entidades nosologicas. De cara al manejo en la urgencia, existen tres pilares fundamentales: tratamiento de soporte, tratamiento sintomatico y, si es posible, tratamiento especifico en funcion de la etiologia.

Introduccion. Las tecnicas de neuroimagen estructural convencional (TC, RM) tienen una utilidad limitada en el diagnostico del paciente parkinsoniano. Por el contrario, las exploraciones de Medicina Nuclear (PET y SPECT) pueden ser herramientas utiles para la evaluacion de estos pacientes, ya que permiten el estudio de aspectos neuroquimicos y funcionales. Objetivo. Revisar el papel de la neuroimagen funcional con PET Y SPECT en el estudio del sistema nigroestriatal y otras funciones cerebrales, con especial hincapie en el SPECT cerebral de transportadores de dopamina con I123-ioflupano, y su utilidad en el diagnostico diferencial de la enfermedad de Parkinson y otros parkinsonismos. Conclusiones. El estudio de la funcion nigro-estriatal y de otros sistemas no dopaminergicos es util para el diagnostico temprano de la enfermedad de Parkinson, incluso en fase promotora; para su diferenciacion del temblor esencial, de otros parkinsonismos no degenerativos (psicogeno, farmacologico, vascular) y de parkinsonismos atipicos (atrofia multisistema, paralisis supranuclear progresiva, degeneracion corticobasal); y para distinguir la enfermedad de Alzheimer de la demencia por cuerpos de Lewy. Otras pruebas y radiotrazadores, para diferentes moleculas-mecanismos que ocurren en la enfermedad de Parkinson y otros parkinsonismos, estan en desarrollo y podrian servir tanto para afinar mas en el diagnostico como para comprender mejor los mecanismos moleculares subyacentes a estas enfermedades y desarrollar nuevas dianas terapeuticas.

Introduccion. La corea consiste en movimientos involuntarios, breves, aleatorios, que pueden afectar a cualquier grupo muscular, fluyendo de forma impredecible de una parte del cuerpo a otra. Los movimientos coreicos estan presentes en reposo, aumentan con maniobras de distraccion, se pueden suprimir parcialmente y con frecuencia desaparecen durante el sueno. El diagnostico diferencial de los sindromes coreicos es muy amplio, incluyendo tanto cuadros de causa genetica como formas adquiridas (enfermedad cerebrovascular y lesiones ocupantes de espacio, coreas de base inmune, coreas de causa infecciosa, encefalopatias toxicas y metabolicas y coreas inducidas por farmacos). Desarrollo. Se revisa la fenomenologia y la fisiopatologia de los movimientos coreicos, las causas mas frecuentes, el proceso diagnostico y las principales novedades en su terapeutica. Conclusiones. La enfermedad de Huntington es la causa mas frecuente de corea hereditaria. En los pacientes con un cuadro familiar sugestivo de enfermedad de Huntington, pero con un estudio genetico negativo, la probabilidad de llegar a un diagnostico definitivo es, a fecha de hoy, muy baja. Los farmacos son la causa mas frecuente de corea adquirida. Ante un caso de hemicorea, es obligado descartar una lesion estructural de los ganglios basales o sus conexiones. El tratamiento de las coreas debe ir encaminado a corregir su causa en el caso de que esta sea reversible, aunque siempre hay que ofrecer un tratamiento sintomatico si la intensidad y la repercusion funcional de la corea asi lo requieren. En las coreas hereditarias se podra hacer prevencion mediante el consejo genetico dirigido a los pacientes afectados y sus familiares.

Hashimoto's autoimmune thyroiditis is a common cause of thyroid disease. Neurological dysfunction related to thyroid hypo or hyperfunction is well known. Not so is autoimmune thyroid disease-associated or Hashimoto's encephalopathy, which includes different neurological manifestations appearing in the context of autoimmune thyroiditis with normal hormone levels. Around fifty cases have been reported since the first description by Brain in 1966. Pathogenesis is unknown, although the most accepted theory points out to an autoimmune cerebral dysfunction. There are two different clinical presentations. The vasculitic type is characterized by relapsing-remitting stroke-like episodes. The diffuse-progressive type shows insidious cognitive impairment, confusion, psychosis, somnolence and coma. Cerebrospinal fluid is abnormal in more than 80% of patients, with high protein levels and mononuclear pleocytosis. Steroids are the treatment of choice, although favourable evolution have been reported spontaneously or after thyroxine treatment.