Chronic Ataxia Research Articles

Prefrontal cortex as a compensatory network in ataxic gait: a correlation study between cortical activity and gait parameters.

To investigate whether prefrontal cortex (PFC) functioning during ataxic gait is linked to compensatory mechanisms or to the typical intra-subject variability of the ataxic gait. Nineteen patients with chronic ataxia and fifteen healthy subjects were evaluated. The subjects were requested to walk along a straight distance of 10 meters while PFC oxygenation and gait parameters were assessed. PFC activity was evaluated by NIRO-200 while gait analysis was performed by the SMART-D500. To investigate the intra-subject variability of gait, we calculated the coefficient of multiple correlation (CMC) of the hip, knee and ankle kinematic waveforms furthermore, we evaluated the step width. We observed a positive correlation between PFC bilateral oxygenation changes and the step width (r = 0.54; p = 0.02 for the right PFC, and r = 0.50; p = 0.03 for the left PFC). No correlation was found between PFC activity and CMC of the hip, knee and ankle waveforms. Our results suggest that PFC activity is linked to gait compensatory mechanisms more than to the variability of the joint kinematic parameters caused by a defective cerebellar control.

Facial Involuntary Movements and Respiratory Failure in CANOMAD, Responsive to IVIG Therapy.

CANOMAD is a rare chronic neuropathy, characterized by chronic sensory ataxia and intermittent brain stem symptoms due to antidisialosyl antibodies. The disorder results in significant morbidity but is poorly understood and often misdiagnosed. We describe a unique case of CANOMAD, associated with involuntary movements of the face; patient reported exacerbations with citrus and chocolate and respiratory muscle weakness. Our patient was initially misdiagnosed with Miller Fisher Syndrome, highlighting the need for vigilance should neurological symptoms recur in patients initially diagnosed with a Guillain Barre variant. Moreover, the optimal treatment is unknown. This patient responded remarkably to intravenous immunoglobulin and has been maintained on this treatment, without further exacerbations.

Drug-Induced Cerebellar Ataxia: A Systematic Review

Cerebellar ataxia can be induced by a large number of drugs. We here conducted a systemic review of the drugs that can lead to cerebellar ataxia as an adverse drug reaction (ADR). We performed a systematic literature search in Pubmed (1966 to January 2014) and EMBASE (1988 to January 2014) to identify all of the drugs that can have ataxia as an ADR and to assess the frequency of drug-induced ataxia for individual drugs. Furthermore, we collected reports of drug-induced ataxia over the past 20 years in the Netherlands by querying a national register of ADRs. Drug-induced ataxia was reported in association with 93 individual drugs (57 from the literature, 36 from the Dutch registry). The most common groups were antiepileptic drugs, benzodiazepines, and antineoplastics. For some, the number needed to harm was below 10. Ataxia was commonly reversible, but persistent symptoms were described with lithium and certain antineoplastics. It is important to be aware of the possibility that ataxia might be drug-induced, and for some drugs the relative frequency of this particular ADR is high. In most patients, symptoms occur within days or weeks after the introduction of a new drug or an increase in dose. In general, ataxia tends to disappear after discontinuation of the drug, but chronic ataxia has been described for some drugs.

Exome sequencing in the clinical diagnosis of sporadic or familial cerebellar ataxia.

Cerebellar ataxias are a diverse collection of neurologic disorders with causes ranging from common acquired etiologies to rare genetic conditions. Numerous genetic disorders have been associated with chronic progressive ataxia and this consequently presents a diagnostic challenge for the clinician regarding how to approach and prioritize genetic testing in patients with such clinically heterogeneous phenotypes. Additionally, while the value of genetic testing in early-onset and/or familial cases seems clear, many patients with ataxia present sporadically with adult onset of symptoms and the contribution of genetic variation to the phenotype of these patients has not yet been established. To investigate the contribution of genetic disease in a population of patients with predominantly adult- and sporadic-onset cerebellar ataxia. We examined a consecutive series of 76 patients presenting to a tertiary referral center for evaluation of chronic progressive cerebellar ataxia. Next-generation exome sequencing coupled with comprehensive bioinformatic analysis, phenotypic analysis, and clinical correlation. We identified clinically relevant genetic information in more than 60% of patients studied (n = 46), including diagnostic pathogenic gene variants in 21% (n = 16), a notable yield given the diverse genetics and clinical heterogeneity of the cerebellar ataxias. This study demonstrated that clinical exome sequencing in patients with adult-onset and sporadic presentations of ataxia is a high-yield test, providing a definitive diagnosis in more than one-fifth of patients and suggesting a potential diagnosis in more than one-third to guide additional phenotyping and diagnostic evaluation. Therefore, clinical exome sequencing is an appropriate consideration in the routine genetic evaluation of all patients presenting with chronic progressive cerebellar ataxia.

Balance exercise in patients with chronic sensory ataxic neuropathy: a pilot study.

Although exercise therapy is considered part of the treatment of neuropathic patients, and somatosensory input is essential for motor learning, performance and neural plasticity, rehabilitation of patients with sensory ataxia has received little attention so far. The aim of this prospective pilot study was to explore the short- and medium-term efficacy of a 3-week intensive balance and treadmill exercise program in chronic ataxic neuropathy patients; 20 consecutive patients with leg overall disability sum score (ODSS-leg) ≥2, absent/mild motor signs, clinical and therapeutic stability ≥4 months were enrolled. Evaluations were done at baseline, at the end of treatment and at 3- and 6-month follow-up. Outcome measurements included: ODSS-leg, Berg balance scale, 6-min walk distance, and the functional independence measure (FIM) scale. The short-form-36 health status scale (SF-36) was used to measure health-related quality of life (HRQoL). ODSS-leg improved significantly compared with baseline, 3 weeks, 3 months (primary outcome), and 6 months follow-up. A significant improvement in all functional secondary outcome measurements and in some SF-36 subscales was also observed. This pilot study suggests that balance exercise is safe and well tolerated and might be effective in ameliorating disability and HRQoL in patients with chronic peripheral sensory ataxia.

Clinical analysis of 15 cases with childhood chronic cerebellar ataxia

Objective To investigate the diagnosis of the diseases that presented with childhood chronic cerebellar ataxia. Method The clinical data of 15 children with chronic cerebellar ataxia were studied, including the clinical features, laboratory results and neuroimaging aspect. Results Of the 15 children with chronic cerebellar ataxia, 3 cases had chronic progressive cerebellar ataxia diagnosed as ataxia telangiectasia, and neuroimaging finding that indicated mild to marked cerebellar atrophy.The others 12 cases had non-progressive cerebellar ataxia, 2 cases of them had Joubert syndrome, characterized by delayed motor function and speech, lower limbs ataxia and cerebellar vermis hypoplasia; 10 cases had ataxic cerebral palsy with delayed motor skills, 9 of them had mental retardation and verbal problem.Of the 10 children with ataxic cerebral palsy, 7 cases had cerebellar hemispheric atrophy by computer tomography (CT) or MRI, while the other 3 cases had no positive finding in cerebellum by MRI, but 2 of whom were found reduced metabolism in cerebellar neuron during the test of positron emission tomography and CT.Comparison with the scores in the gross motor function measure(GMFM) and developmental quotient (DQ) of 5 domains(adaption, gross motor, fine motor, language and social development)in Gesell developmental Schedules before and after the rehabilitation approach: the totaI scores in GMFM after the treatment (56.42±15.65) was significantly higher than that of before treatment(44.15±20.41) (t=-3.121, P 0.05). Conclusions Children with chronic cerebellar ataxia presented as hypotonia with delayed motor function, and ususlly had inherent cerebellum abnormalities, without matter structure or function of the neuron.Chronic ataxia is an important symptom in genetic or metabolic disease, and a systematic approach may enhance diagnostic accuracy. Key words: Cerebellar ataxia; Ataxia telangiectasia; Cerebral palsy; Child

Antiphospholipid Antibodies and Cerebellar Ataxia: A Clinical Analysis and Literature Review

Background: Although it has been established that antiphospholipid antibodies (APAbs) bind to and modulate the signaling of cerebellar neurons in vitro, the clinical correlation between increased APAbs and cerebellar ataxia has rarely been investigated. Methods: We reviewed 10 patients presenting with cerebellar ataxia with increased blood APAbs from our database along with 3 APAb-associated cerebellar ataxia patients in the literature. Results: Of these 10 patients, 4 exhibited a subacute onset of progressive ataxia, and there were no significant structural changes in their brains that appeared to be responsible for the symptoms. Another 6 showed a chronic course of ataxia, and shared similar morphological changes that included symmetrical lesions in bilateral hemispheres, periventricular lucency and central and temporal atrophy of varying severity; the cerebellum was spared. The predominant APAbs for subacute and chronic ataxia were the anti-beta₂-glycoprotein I antibody and anticardiolipin antibody, respectively. Cancer was found in 1 patient with subacute ataxia and in 4 with chronic ataxia. The removal of the cancer, the plasmapheresis and immunosuppressive therapy successfully abolished the ataxia and increased APAb levels in all 5 patients. Conclusions: The relation between APAbs and nonvascular neurological disorders, such as cerebellar ataxia, should be further studied. APAbs may mediate neurological deficits via different mechanisms such as structural damage or functional neurotoxicity. Clinically, the examination of blood APAb levels is recommended for patients with cerebellar ataxia without a determined cause, and the further survey of systemic cancers in the case of APAb positivity is also recommended. Finally, plasmapheresis is a reasonable and effective treatment for APAb-associated cerebellar ataxia.

Ethnicity and Geographic Distribution of Pediatric Chronic Ataxia in Manitoba

Genetic and environmental factors are important determinants of disease distribution. Several disorders associated with ataxia are known to occur more commonly in certain ethnic groups; for example, the disequilibrium syndrome in the Hutterites. The aim of this study was to determine the ethnic and geographic distribution of pediatric patients with chronic ataxia in Manitoba, Canada. We identified 184 patients less than 17 years-of-age with chronic ataxia during 1991-2008 from multiple sources. Their diagnosis, ethnicity and place of residence were determined following a chart review. Most patients resided in Manitoba (N=177) and the majority in Winnipeg, the provincial capital. Thirty five Aboriginal, 29 Mennonite and 11 Hutterite patients resided in Manitoba. The latter two groups were significantly overrepresented in our cohort. Ataxia telangiectasia, mitochondrial disorders, and non-progressive ataxia of unknown etiology associated with pyramidal tracts signs and developmental delay were significantly more common in Mennonite patients. Four of five patients with neuronal migration disorders associated with chronic ataxia were Aboriginal. Few isolated disorders with chronic ataxia occurred in the 11 Hutterite patients including a Joubert syndrome related disorder. Three disorders associated with chronic ataxia were more prevalent than expected in Mennonites in Manitoba. Few rare disorders were more prevalent in the Hutterite and Aboriginal population. Further research is needed to determine the risk factors underlying these variations in prevalence within different ethnic groups. The unique risk factor profiles of each ethnic group need to be considered in health promotion endeavors.

RETROBULBARINIS PSEUDOTUMORAS DĖL SKRUOSTE UŽSILIKUSIO SMULKAUS METALINIO SVETIMKŪNIO: KLINIKINIO ATVEJO APRAŠYMAS IR LITERATŪROS APŽVALGA

Aim: to present a patient’s clinical case; to demonstrate how important is to suspect rertrobulbar pseudotumor timely, why it is necessary to remove even the smallest metal foreign bodies from the jaw area; to show the importance of an integrated simultaneous clinical delivery on the spot during the investigation of a complex illness. Case report: presenting the clinical case – patient MA (66 years of age) right eye vision started to deteriorate 6 years ago, a small defect of a pupil (abnormal pupil shape) was found; after the remove a cataract operation, the vision improved (during the week after the operation the patient has not used prescribed corticosteroid drops in the eye, this incompliance with prescription caused the uveitis anterior, which went away in 2 months after relevant treatment started). One year after surgery a pain appeared in the area of the right cheek, teeth and beneath the right eye, manifested hearing weakness dextra side. Several dentists treated this patient. Also rhinologist, mouth, face, jaw surgeons and oncologists were involved. Diagnosis: alveolitis, sinusitis, osteomielitis sinus maxilaris dextra, a foreign body in a right maxillary sinus projection. Patient was examined for TBC, sarcoidosis, fungal illness, syphilis, all with negate results. Gradually right eye became blind. After the vision of the left eye began to deteriorate, further cataract surgery was undertaken. The further sudden deterioration in the general condition of the patient was treated in the neurological and supportive therapy departments for several months. Diagnosis: cerebellar degeneration and chronic polyneuropathy ataxia, unspecified dementia, extraocular palsies, metabolic hepatitis, chronic pancreatitis, bladder disturbance. During that time a protrusion of the right eye gradually enlarged and became more exposed. The left eye became blind several months later. KT and MRT: right eye’s retrobulbar tumor spread through eyehole slots intracranial and to left orbit; a small metal foreign body was found subcutaneously in the right cheek. A biopsy was taken from the para- and retrobulbar tissues: fibromatosis was diagnosed. Half a year later a sphenoorbital meningioma was suspected and the surgery aimed to partially remove a tumor from the right orbit was performed. During this stay under the neurosurgeons care it becomes clear that episodes of psychomotor agitation were also present. The eyelids of the right eye were sutured to protect the cornea against perforation. Histologic diagnosis: retrobulbar pseudotumor of both eyes. Metal foreign body remained untouched. The ophthalmologist removed the foreign metal body, which was situated in the cheek subcutaneously, close to N. infraorbitalis with capsule in a local polyclinic soon afterwards. The composition of the foreign metal object was investigated: it was found that 95% of it was iron with small amounts of rare metals usually found in steel alloy, calcium. Histology detected hemosiderosis in connective tissue of capsule. Patient was examined by a rheumatologist on the basis of the suspicion of Wegener granuliomatosis. Data to confirm Wegener’s granulomatosis was not enough; internal organs without lesions, it was diagnosed cholelithiasis and fibrotic lesions in the lungs. It was confirmed systemic transgression of connective tissue with retrobulbar pseudotumor diagnosis. Corticosteroid treatment was given for 1 month. Patient was examined 8, 15 and 27 month after foreign body removal later: the skin of the face was free of scars, eyelids of the right eye has been sutured; the left eye had no inflammation, refracto- and keratometry findings were the same, like 4 years before; levels of immunoglobulins G and E in blood decreased - normal; the systemic transgression of connective tissue remained. Patient walks with a wide-based gait, he becames totally dependent on care (he is blind and desorientated at place and time, his personality has changed; Mini Mental State Examination 13/30). This story showed, how it is important to have a complete understanding of the patients health from various medical specialists at the same physical place and at the same time. The case shows surprising differences of results of radiologic examination of the same case.

Experience in a short-term trial with 4-Aminopyridine in cerebellar ataxia

4-Aminopyridine (4-AP) is a reversible blocker of voltagegated potassium channels. Its slow release form has been approved for symptomatic treatment of gait disorder in multiple sclerosis [2]. In a number of small studies, 4-AP and the related compound 3,4-diaminopyridine (3,4-AP) improved downbeat nystagmus and reduced attack frequency in episodic ataxia [9]. In addition, 4-AP decreased gait variability in patients with chronic cerebellar ataxia of different origin [7, 8]. Chronic treatment with 3,4-AP had beneficial effects in a mouse model of spinocerebellar ataxia type 1 (SCA1) [3]. We here report our clinical experiences with 4-AP in 16 patients with chronic cerebellar ataxia. As 4-AP is thought to exert its effect on ataxia by interfering with the activity of cerebellar Purkinje neurons, we treated patients with SCA1, SCA3, SCA6 and sporadic adult-onset ataxia of unknown origin (SAOA), as well as one with a POLG mutation. These disorders are characterized by prominent cerebellar cortical degeneration with Purkinje cell involvement. Three centers participated in the observations. After giving informed consent, 16 patients were treated with the slow release form of 4-AP (Fampyra , 2 9 10 mg/day). Nine of the patients were female. Three patients were diagnosed SCA1, three SCA6, two SCA3, one genetically nonidentified autosomal dominant cerebellar ataxia, one POLG mutation and six of them a SAOA. Age was 60 ± 11.3 years (mean ± SD), disease duration 16.3 ± 17.1 years. To assess the severity of ataxia, we used the Scale for the Assessment and Rating of Ataxia (SARA) [5]. In addition, patients underwent three timed coordination tests, the 8 m walk (8 MW), the 9-hole pegboard (9HPT), and the speech rate test (PATA rate). Performance in these tests allows calculating the SCA Functional Index (SCAFI) [6]. Results of the timed tests are expressed as Z scores. Neurological symptoms other than ataxia were assessed with the Inventory of Non-Ataxia Signs (INAS) [4]. Patients estimated their health-related quality of life on the visual analogue scale of the EQ-5D (EQ-VAS) [1]. Assessments were done at baseline, 4 h and 14 days after treatment. Although two patients discontinued 4-AP due to side effects, the compound was generally well tolerated. This view is also supported by the trend towards an improvement of the EQ-VAS after 14 days. In the remaining 14 patients, SARA (range: 0–40) improved from 14.3 ± 4.7 to 13.0 ± 4.6 points after 4 h (n = 11) and to 13.7 ± 4.6 points after 14 days (n = 14), but these differences failed I. Giordano (&) H. Jacobi M. Minnerop T. Klockgether Department of Neurology, University Hospital of Bonn, Sigmund-Freud-Strase 25, 53105 Bonn, Germany e-mail: ilaria_anna.giordano@ukb.uni-bonn.de

Distraction-stabilisation of two adjacent intervertebral spaces in a Dalmatian dog with caudal cervical spondylomyelopathy

A 4-year-old, 40-kg, male, entire Dalmatian was presented for evaluation of chronic neck pain and pelvic limb ataxia. Myelography revealed ventrodorsal (hourglass) extradural compression over the intervertebral space between the 5th and 6th cervical vertebra and ventral extradural compression between the 6th and 7th cervical vertebra. Cranial compression disappeared and caudal compression markedly diminished after performing cervical traction. MRI scan confirmed protrusion of intervertebral discs and spinal cord compression in previously mentioned intervertebral spaces. Surgical distraction-stabilization of both intervertebral spaces was performed using threaded pins and polymethylmethacrylate. The convalescence from surgery was uneventful and the dog was walking without any signs of paresis until 5 months after surgery when radiography revealed implants loosening. The dog recovered fully of the implant removal and remained asymptomatic for more than 30 months.

The epidemiology of intermittent and chronic ataxia in children in Manitoba, Canada

To determine the epidemiology of chronic ataxia in children in Manitoba, Canada. A retrospective study using multiple sources and disease codes identified children (age 0-16y) with chronic ataxia (>2mo duration or recurrent episodes of ataxia) seen at Winnipeg Children's Hospital from 1991 to 2008. Patients with isolated peripheral nerve diseases, vestibular disorders, or brain tumors were excluded. We identified 184 patients (males=females; mean age 15y, SD 7y 8mo) with chronic ataxia. Median age at the presenting symptom onset was 1 year 3 months and at ataxia onset 3 years 1 month. Median duration of follow-up was 6 years 5 months. During the study period, the crude incidence rate was 5.77 in 10,000; the crude prevalence rate was 6.59 in 10,000; and the crude mortality rate 0.446 in 10,000. The most common presenting symptoms were developmental delay, ataxia, or seizures. The most common diagnoses (known in 129) were Angelman syndrome (n=16), ataxia telangiectasia (n=13), mitochondrial disease (n=9), Friedreich ataxia (n=7), stroke (n=7), and familial/genetic episodic ataxia (n=7). Chronic ataxia is a relatively common early-presenting symptom in childhood. A specific diagnosis is possible in 70% of patients after extensive investigations. The mortality rate is relatively low and the disease burden is high with significant comorbidities including developmental delay and epilepsy.

Chronic childhood ataxia: the cause depends on how you look

This commentary is on the original article by Salman et al on pages 341–347 of this issue.

Familial and Sporadic Hemiplegic Migraine: Diagnosis and Treatment

Hemiplegic migraine (HM) is a rare subtype of migraine with aura, characterized by transient hemiparesis during attacks. Diagnosis is based on the International Classification of Headache Disorders criteria (ICHD-II). Two types of HM are recognized: familial (FHM) and sporadic hemiplegic migraine (SHM). HM is genetically heterogeneous. Three genes have been identified (CACNA1A, ATP1A2, and SCN1A) but more, so far unknown genes, are involved. Clinically, attacks of the 3 subtypes cannot be distinguished. The diagnosis can be confirmed but not ruled out by genetic testing, because in some HM patients other, not yet identified, genes are involved. The presence of additional symptoms (such as chronic ataxia or epilepsy) may increase the likelihood of identifying a mutation. Additional diagnostics like imaging, CSF analysis, or an EEG are mainly performed to exclude other causes of focal neurological symptoms associated with headache. Conventional cerebral angiography is contraindicated in HM because this may provoke an attack. Because HM is a rare condition, no clinical treatment trials are available in this specific subgroup of migraine patients. Thus, the treatment of HM is based on empirical data, personal experience of the treating neurologist, and involves a trial-and-error strategy. Acetaminophen and NSAIDs often are the first choice in acute treatment. Although controversial in HM, triptans can be prescribed when headaches are not relieved sufficiently with common analgesics. An effective treatment for the severe and often prolonged aura symptoms is more warranted, but currently no such acute treatment is available. Prophylactic treatment can be considered when attack frequency exceeds 2 attacks per month, or when severe attacks pose a great burden that requires reduction of severity and frequency. In no strictly preferred order, flunarizine, sodium valproate, lamotrigine, verapamil, and acetazolamide can be tried. While less evidence is available for prophylactic treatment with topiramate, candesartan, and pizotifen, these drugs can also be considered. The use of propranolol in HM is more controversial, but evidence of adverse effects is insufficient to contraindicate beta-blockers.

Case Report of Subacute Cerebellar Ataxia of Adolescence With Long-Term Sequelae

Acute ataxia is not an uncommon childhood complaint. It most commonly occurs in young patients secondary to a postinfectious cerebellitis, which is typically associated with a very good prognosis and recovery. In adolescence, acute cerebellar ataxia is more often the product of an etiology likely to progress into a chronic disorder without recovery to preillness baseline. In the present case, the authors describe a 15-year-old girl with subacute cerebellar ataxia of presumed immune-mediated etiology that advanced into a chronic cerebellar ataxia. Due to a family history, celiac disease was suspected as the origin of the ataxia; biopsy ruled out enteropathy, and the severe, abrupt radiological changes to the patient's cerebellum are inconsistent with the reported sequelae of gluten ataxia. This case serves as a discussion for diagnostic challenges in adolescent patients with acute cerebellar ataxia with long-term sequelae as well as providing an adjunct discussion on the neurological complications of celiac disease.

GM2 Gangliosidosis in an Adult Pet Rabbit

A 1.5-year-old neutered male rabbit was presented with chronic nasal discharge and ataxia. Rapid progression of neurological signs was noted subsequent to general anaesthesia and the rabbit was humanely destroyed due to the poor prognosis. At necropsy examination there were no gross changes affecting the brain or spinal cord. Microscopical examination revealed that the perikarya of numerous neurons in the brain and spinal cord were distended by the intracytoplasmic accumulation of pale, finely granular to vacuolar material. Transmission electron microscopy showed this to be composed of concentric membranous cytoplasmic bodies. Thin layer chromatography revealed elevation of GM2 ganglioside in the brain of this rabbit compared with that of an unaffected control rabbit. Enzymatically, there was markedly reduced activity of tissue β-hexosaminidase A in brain and liver tissue from the rabbit. This was a result of an almost complete absence of the enzymatic activity of the α-subunit of that enzyme. These findings are consistent with sphingolipidosis comparable with human GM2 gangliosidosis variant B1.

Leukodystrophies in Patients with Adult-Onset Ataxia: Frequency and Phenotype (P05.020)

Objective: We aimed to determine the frequency of leukodystrophies and its phenotypic spectrum in patients with ataxia of unknown cause. Background A broad spectrum of heterogeneous neurological disorders including lysosomal storage disorders present with chronic progressive cerebellar ataxia. Identifying the underlying etiology is important as it sometimes allows for initiation of pharmacological treatment. Design/Methods: We prospectively studied 107 index patients who presented with adult-onset cerebellar ataxia consistent with autosomal recessive inheritance. Patients were screened for lysosomal enzyme deficiencies including metachromatic leukodystrophy, GM1-Gangliosidosis, Tay-Sachs and Sandhoff9 disease, and Krabbe disease. If clinical evidence was suggestive of other types of leukodystrophies, additional genetic or metabolic testing was performed. Clinical characterization included neurological and psychiatric features and MR-imaging. Results: Screening for lysosomal disorders detected one patient with late-onset Tay Sachs disease and one with metachromatic leukodystrophy. Both patients presented with cognitive deficits and psychiatric comorbidity beside ataxia. Additonal tests revealed two patients with Nieman Pick disease type C, one with cerebrotendinous xanthomatosis, and one with leukencephalopathy with brain stem and spinal cord involvement and lactate elevation. All of them presented with additional signs like cognitive dysfunction, pyramidal affection and/or peripheral neuropathy. Conclusions: Leukodystrophies were responsible for 6% of cryptic ataxia in our series. The concomitant occurrence of cerebellar ataxia with cognitive dysfunction, psychiatric comorbidities, spasticity and/or neuropathy should prompt screening for lysosomal storage disorders. Hyperintensity of cerebral white matter on MR FLAIR images is not an obligate marker in adult-onset leukodystrophies. Supported by: German Ministry of Research and Education (BMBF) grant 01GM0838. Disclosure: Dr. Muller vom Hagen has nothing to disclose. Dr. Synofzik has received personal compensation for activities with Volkswagen Foundation, the Movement Disorder Society, and Fresenius Kabi. Dr. Schicks has nothing to disclose. Dr. Krageloh-Mann has nothing to disclose. Dr. Schoels has received research support from Deutsche Forschungsgemeinschaft, German Research Council, Leukonet, mitoNET, EUROSPA, RISCA, and the HSP-Selbsthilfegruppe Deutschland eV.

Ataxie révélant un déficit constitutionnel en vitamine E

Ataxia which is caused by deficiency of vitamin E is an inherited neurodegenerative disorder characterized by impaired ability of coordinate voluntary movements (ataxia) and rare peripheral neuropathy. The responsible gene is located on the long arm of chromosome 8. In the absence of replacement therapy, neurological signs worsen with loss of autonomy. The clinical picture is very similar to Freidreich’s ataxia but there is a cure for deficiency of vitamin E. Ataxia. We report a case of a 14 years old patient of consanguineous parents hospitalized for chronic ataxia. The symptoms started 18 months earlier with a progressive gait disturbances, and balance and hand tremor, dysarthrie, without gastrointestinal symptoms. Clinical examination showed a thracolumbar scoliosis. And pes cavus, neurological examination noticed a kinetic ataxia, absence of tendon reflexes. There was no failure to thrive. The ophthalmologic examination was without abnormalities. The determination of vitamin E level in the blood was low up to 2 pmol/l (N: 16-53 pmol/l). The child has a long term oral vitamin E treatment, and the evolution was marked after two years by an improvement of clinical signs, biological and radiological signs with stoppage of the disease progression. In any case of phenotype Freidreich chronic ataxia, we recommend performing a systematic determination of serum vitamin E level.

Prefrontal cortex controls human balance during overground ataxic gait

1) to verify if prefrontal cortex (PFC) is activated during over ground walking in ataxic patients, 2) to correlate the clinical parameters of gait with the PFC activation patterns. Fourteen patients and 20 healthy subjects were studied. Ataxia was assessed by the Scale for the Assessment and Rating of Ataxia (SARA). A 2-channel near-infrared system was used to investigate the changes in oxygenated ([O2Hb]t) and deoxygenated ([HHb]t) hemoglobin concentrations on the PFC during gait. [O2Hb] baseline-corrected activation values ([O2Hb]c) were calculated by the difference between [O2Hb]t and [O2Hb] during upright posture ([O2Hb]b). [O2Hb]t was increased for both channels (respectively p < 0.01 and p = 0.01) only in the patients. No variation was observed in [HHB]t. The correlation coefficient between [O2Hb]c and the SARA gait score was respectively r: 0.878 (p < 0.01) and r: 0.839 (p < 0.01) for the right and left PFC, between [O2Hb]c and the SARA stance score respectively r: 0.893 (p < 0.01) and r: 0.832 (p < 0.01). During over ground gait PFC is bilaterally activated in patients with severe chronic ataxia. These findings may be associated with compensatory mechanisms which are involved in severe conditions when other nervous centers controlling balance are functionally not efficient.

Acute Striatal Necrosis in Hemiplegic Migraine With de Novo CACNA1A Mutation

We report the case of a 9-year-old girl with early-onset developmental delay, chronic ataxia and prolonged hemiplegic migraine episodes bringing about progressive deterioration. Two days into one episode, diffusion-weighted magnetic resonance imaging disclosed unilateral striatal abnormal signal consistent with cytotoxic edema, which evolved into atrophy on follow-up scans. Mutational screen of CACNA1A gene identified a de novo p.Tyr1387Cys mutation.