Chronic Ataxia Research Articles

Treatment of refractory trigeminal neuralgia with intravenous phenytoin

The case of a patient who was successfully treated with i.v. phenytoin for an acute exacerbation of refractory trigeminal neuralgia (TN) is reported. A 77-year-old, 87-kg Caucasian man with a 12-year history of right-sided, classical TN was admitted for an acute exacerbation of TN refractory to pharmacologic treatment with carbamazepine, baclofen, hydrocodone-acetaminophen, tramadol, hydromorphone, and gabapentin. His medical history included atrial fibrillation, peripheral vascular disease, benign prostatic hyperplasia, and chronic ataxia secondary to antibiotic therapy in the 1970s. His outpatient medications included carbamazepine, warfarin, ergocalciferol, and saw palmetto. A 15-mg/kg dose of i.v. phenytoin sodium (1300 mg on the basis of total body weight) was recommended by neurology consultants. Because of potential adverse reactions related to high serum phenytoin concentrations and rapid infusion rates (e.g., hypotension, ataxia, nausea, vomiting, apnea, nystagmus), the patient's age, the baseline presence of atrial fibrillation and ataxia, and the fact that seizures were not being treated, the clinical pharmacist recommended dividing the 1300-mg dose into two 650-mg doses separated by four hours, with each infused at 25 mg/min; this suggestion was accepted. The patient's pain score dropped from a self-rated 12/10 to 2/10 after the first infusion and to 1/10 after completion of the second infusion. The patient's blood pressure and heart rate were monitored via telemetry every five minutes during both infusions. No adverse events were noted. Phenytoin sodium 15 mg/kg i.v. divided into two doses separated by four hours was safe and effective in treating an acute exacerbation of refractory TN.

Superficial Siderosis of the CNS and Otoneurological Manifestations

Superficial siderosis is an uncommon condition occurring in central nervous system (CNS) due to deposition of hemosiderin in the subpial meningeal layer causing progressive neurological dysfunction. The classical clinical manifestation is a triad of chronic ataxia, bipyramidal signs and progressive bilateral symmetrical sensorineural hearing loss (SNHL). It has rarely been reported in Indian literature. We report an unusual case of superficial siderosis in a 60-year-old farmer who presented with the above triad along with involvement of olfactory nerve. We present this case to highlight the fact that progressive SNHL can be an important sign for the early awareness of this rare disorder. The literature on superficial siderosis is reviewed and the pathogenesis is discussed.

Midbrain Cleft as a Cause of Chronic Internuclear Ophthalmoplegia, Progressive Ataxia, and Facial Weakness

A 44-year-old man with progressive ataxia, facial weakness, bilateral adduction deficits, and abducting nystagmus was initially misdiagnosed and treated for multiple sclerosis because a midbrain anatomic cleft had been overlooked on brain MRI. Six cases of "midbrain (or mesencephalic) cleft" or "keyhole aqueduct syndrome" have been previously reported. This developmental anatomic abnormality always manifests bilateral internuclear ophthalmoplegia (INO), often together with ataxia, which may be progressive and debilitating. Because the INO is chronic, patients may have no visual symptoms. The cause of a midbrain cleft is uncertain, but it may be the midbrain version of a syrinx. There is no known effective treatment.

Riluzole in cerebellar ataxia

The pleiotropic effects of riluzole may antagonize common mechanisms underlying chronic cerebellar ataxia, a debilitating and untreatable consequence of various diseases. In a randomized, double-blind, placebo-controlled pilot trial, 40 patients presenting with cerebellar ataxias of different etiologies were randomly assigned to riluzole (100 mg/day) or placebo for 8 weeks. The following outcome measures were compared: proportion of patients with a decrease of at least 5 points in the International Cooperative Ataxia Rating Scale (ICARS) total score after 4 and 8 weeks compared with the baseline score; mean changes from the baseline to posttreatment ICARS (total score and subscores at 8 weeks); and occurrence of adverse events. Riluzole and placebo groups did not differ in baseline characteristics. The number of patients with a 5-point ICARS drop was significantly higher in the riluzole group than in the placebo group after 4 weeks (9/19 vs 1/19; odds ratio [OR] = 16.2; 95% confidence interval [CI ] 1.8-147.1) and 8 weeks (13/19 vs 1/19; OR = 39.0; 95% CI 4.2-364.2). The mean change in the riluzole group ICARS after treatment revealed a decrease (p < 0.001) in the total score (-7.05 [4.96] vs 0.16 [2.65]) and major subscores (-2.11 [2.75] vs 0.68 [1.94] for static function, -4.11 [2.96] vs 0.37 [2.0] for kinetic function, and -0.74 [0.81] vs 0.05 [0.40] for dysarthria). Sporadic, mild adverse events occurred. These findings indicate the potential effectiveness of riluzole as symptomatic therapy in diverse forms of cerebellar ataxia. This study provides Class I evidence that riluzole reduces, by at least 5 points, the ICARS score in patients with a wide range of disorders that cause cerebellar ataxia (risk difference 63.2%, 95% CI 33.5%-79.9%).

The Effect of Prostaglandin E1 and Prednisolone on Chronic Pain and Ataxia in a Patient with Aortitis Syndrome

The Effect of Prostaglandin E1 and Prednisolone on Chronic Pain and Ataxia in a Patient with Aortitis Syndrome

Spinal dermoid sinus in a Burmese cat with paraparesis

A 2-year-old, male, Burmese cat was evaluated for chronic progressive hindlimb weakness, ataxia and urinary incontinence. Radiographic examination, myelography and magnetic resonance imaging defined congenital vertebral anomalies and a space-occupying intradural, extramedullary mass. A dermoid sinus was subsequently identified dorsal to the affected spine. Surgical excision of the tract necessitated a dorsal laminectomy and removal of a 1-cm diameter intradural dermoid sinus 'cyst' that contained hair and sebaceous debris. The cat recovered hindlimb function after surgery and remains asymptomatic 50 months after surgery except for a persistent inability to urinate voluntarily.

Rare Autosomal Dominant POLG1 Mutation in a Family With Metabolic Strokes, Posterior Column Spinal Degeneration, and Multi-Endocrine Disease

DNA POLG is the only mitochondrial DNA polymerase and is encoded by nuclear DNA. Depending on the location and inheritance, mutations in POLG1, the catalytic subunit, can cause symptoms including severe infantile epilepsy, metabolic strokes, chronic ataxia, neuropathy, and ophthalmoplegia. We reviewed medical records and conducted extensive interviews with the family of identical twin probands with a mutation in the linker region of DNA polymerase gamma 1 (POLG1) (G517V) and discuss postmortem findings from their grandmother. Both twins developed type I diabetes, adrenal insufficiency, hypothyroidism, and psychiatric problems in addition to neurological difficulties including bilateral basal ganglia infarcts, headaches, and seizures. The maternal grandmother, now deceased, had psychosis and balance problems, and postmortem findings include lacunar infarcts in the basal ganglia (caudate nucleus, putamen, and globus pallidus) and posterior spinal column degeneration. We discuss novel aspects of their presentation and implications for practice.

The genetic aetiology of late-onset chronic progressive cerebellar ataxia

An increasing number of dominant and recessive disorders have been associated with late onset chronic progressive ataxia (LOCA) complicating the formulation of a rational diagnostic strategy. Furthermore, there is marked geographic and ethnic variation in the relative importance of these individual disorders and the cause of such observed variation remains unexplained. We have systematically investigated a population-based cohort of patients with chronic progressive LOCA for SCA 1, 2, 3, 6, 7, 8, 10, 12, 17, FXTAS and FRDA. In addition we have examined repeat length polymorphism in chromosomes from a genetically homogeneous and representative control population to investigate the association of high-normal repeats and disease prevalence. A total of 178 patients including 55 familial cases segregating in 38 kindreds and 123 sporadic were investigated. Pathological expansions were identified in 11/38 (28.9 %) of families and in 5/123 (4.1 %) of sporadic patients. The most frequent diagnoses were SCA6 (6 families and 1 sporadic patient), DRPLA (4 families) and SCA8 (1 family). In addition, one elderly female patient was identified with "possible FXTAS". Six (2 %) control patients were noted to have expanded SCA8 alleles. SCA6 and DRPLA were the most frequent genetic diagnoses identified. Patterns of high-normal allele frequency in this UK population were distinct compared to other ethnic groups but this was poorly predictive of the distribution of disease in this region. The relative contribution of new mutation formation and founder effects to the prevalence of familial ataxia is uncertain, and further exploration of these factors will require detailed analysis of disease allele haplotypes and meiotic instability of intermediate length alleles.

Electromyographic recordings of slow leg tremor in chronic alcoholics.

Certain features of the slow leg tremor observed in chronic alcoholic ataxia were established by electromyographic recordings. In standing (Romberg's test) the recordings from the flexor and extensor muscles of the feet showed a 3 Hz regular, alternating tremor of high intensity. The tremor activity was synchronous in the right and left legs. A similar slow tremor could also, in certain attitudes, be recorded from other muscle groups in the legs and, rarely, in the upper limbs.

Diagnostic Exercise: Epithelioid Hemangiosarcoma Mimicking Metastatic Prostatic Neoplasia in a Dog

A 10-year-old intact male Labrador Retriever dog was euthanized because of rapid deterioration after suffering from mild chronic cough, hematuria, acute blindness, ataxia, and lethargy. Clinical examination revealed blepharospasm and hyphema, with clear discharge from the right eye; a firm mass in an enlarged right testicle; a mass in the irregularly enlarged prostate; and nodules in the left kidney, liver, and spleen detected by abdominal sonography. Cytologic evaluation of fine needle aspirates from the prostate, testis, and kidney comprised large, clustered or individualized, anaplastic cells that lacked convincing tissue differentiation. Necropsy examination revealed an irregularly enlarged prostate with dark tan to red zones and multiple, discrete, beige to dark red nodules that ranged from 0.5 to 6 cm in diameter in the lung, liver, left kidney, right testis, colon wall, stomach wall, and brain. On histologic examination, discrete nests of anaplastic carcinoma-like tumor cells were found in sections of all affected organs. Results of immunohistochemical examination revealed widespread expression of von Willebrand factor and the absence of cytokeratin in neoplastic cells. The diagnosis was metastatic epithelioid hemangiosarcoma, primary site unknown.

A case of chronic recurrent cerebellar ataxia responding to steroid therapy

We present a 25-month-old female having unusual cerebellar ataxia responsive to steroid therapy. She had suddenly suffered from action tremor and trunkal ataxia, following antecedent mild respiratory infection. These symptoms lasted for a month, and therefore she was referred to our hospital. No abnormal findings were disclosed for cerebrospinal fluid or MR images, but anti-glutamate receptor δ2 antibodies were detected in serum. MR spectroscopy of the cerebellum revealed a decrease in the N-acethylasparate/creatine ratio, suggesting micro-neuronal damage. She had quickly responded to high-dose methylpredonisolone therapy and the effectiveness of this steroid was reproducible in the subsequent relapses of ataxia. This clinical course seemed to be unique and was characterized as chronic recurrent cerebellar ataxia responding to steroid therapy.

Chronic sensorimotor polyradiculopathy with antibodies to P2: An electrophysiological and immunoproteomic analysis

In this study we report a patient with chronic progressive sensory ataxia, proximal weakness, immunoglobulin M (IgM) monoclonal gammopathy, and elevated protein levels in the cerebrospinal fluid, who showed a good response to prednisone. Electrophysiological study disclosed abnormalities predominantly of late responses (F waves and H reflexes), with no evidence of demyelination in the peripheral nerves, suggesting motor and preganglionic sensory nerve roots as the site of the lesion. An immune-mediated pathogenesis was considered and, to identify possible target antigens, we performed bidimensional electrophoresis and a Western blot study. Based on the suspected lesion site, we used human anterior and posterior root extracts. We identified IgM reactivity against peripheral nerve myelin protein P2. Enzyme-linked immunosorbent assay confirmed IgM reactivity toward one synthetic peptide from P2. To our knowledge, reactivity against P2 has not been reported previously in a paraproteinemic neuropathy. Furthermore, we demonstrated that bidimensional electrophoresis and Western blot of the tissue involved, as determined by clinical and electrophysiological studies, may be useful to establish clinical-immunological correlations in paraproteinemic neuropathies.

Neurophysiological investigation of a chronic sensory ataxia

Neurophysiological investigation of a chronic sensory ataxia

Treadmill training for ataxic patients: a single-subject experimental design

Objective: To investigate changes in gait quality, balance and mobility associated with treadmill training for ataxic individuals. Design: Single-subject ABA design. Baseline phases (A) lasted three weeks and intervention (B) lasted four weeks. Setting: University rehabilitation clinic. Subjects: A woman (25 years) and a man (53 years) with chronic ataxia due to head trauma. Intervention: Three 20-minute treadmill training sessions each week with progression in velocity and step length. Main measures: Rivermead Visual Gait Assessment, Timed Up and Go, time to complete a balance task, walking speed, cadence, and stride length assessments three times a week during the 10 weeks. Data were analysed with the celeration line technique and two standard deviation band. Results: Both individuals demonstrated gains in all parameters over initial baseline and subsequent phases, with performance increases ranging from 26% to 233% when first and last assessments were compared. Significantly superior effects of treadmill training over baseline conditions on cadence were detected (P<0.05). Gains in walking speed were not significantly better during intervention, but intervention withdrawal produced deceleration of performance gains. Gains in Timed Up and Go, step length and balance were not consistent and were possibly caused by a learning effect of the association between repeated testing and treadmill training. Rivermead Visual Gait Assessment gains reached significance only for subject 2 (P<0.05), probably because of increased variability of performance of subject 1. Results suggest that the association between repeated testing and treadmill training might have been responsible for the observed gains in the two ataxic patients.

Early onset progressive ataxia associated with the first CACNA1A mutation identified within the I–II loop

Familial hemiplegic migraine type 1, spinocerebellar ataxia type 6 (SCA6) and episodic ataxia type 2 (EA2) are allelic disorders associated with mutations in the CACNA1A gene, which encodes the alpha1 subunit of the P/Q-type calcium channel (Ca(V)2.1). SCA6 and EA2 share a number of clinical features, such as prominent cerebellar involvement and good response to acetazolamide therapy. However, while SCA6 develops as a late-onset, progressive ataxia, EA2 has an earlier, and episodic, onset. We report on two sisters with a heterogeneous clinical phenotype. The first developed progressive cerebellar ataxia after age 30, without noticeable episodes of vertigo or headache. A 1 year trial with acetazolamide did not produce significant results. The other reported episodes of vertigo, headache and gait imbalance since late childhood, with good response to acetazolamide, before developing moderate chronic cerebellar ataxia. Brain MRI showed cerebellar atrophy, especially in the vermis, in both patients. Direct sequencing of CACNA1A identified a heterozygous 1360G>A mutation in exon 11 resulting in the substitution of alanine for threonine at residue 454 (p.Ala454Thr). This is the first description of a change residing in the cytoplasmic I-II loop associated with a clinical phenotype.

Chronic cerebellar ataxia and hereditary hemochromatosis: causal or coincidental association?

Chronic cerebellar ataxia and hereditary hemochromatosis: causal or coincidental association?

Early-onset progressive ataxia associated with the first CACNA1A mutation identified within the I–II loop

Familial hemiplegic migraine type 1, spinocerebellar ataxia type 6 (SCA6) and episodic ataxia type 2 (EA2) are allelic disorders associated with mutations in the CACNA1A gene, which encodes the α1 subunit of the P/Q-type calcium channel (Ca V2.1). SCA6 and EA2 share a number of clinical features, such as prominent cerebellar involvement and good response to acetazolamide therapy. However, while SCA6 develops as a late-onset, progressive ataxia, EA2 has an earlier, and episodic, onset. We report on two sisters with a heterogeneous clinical phenotype. The first developed progressive cerebellar ataxia after age 30, without noticeable episodes of vertigo or headache. A 1 year trial with acetazolamide did not produce significant results. The other reported episodes of vertigo, headache and gait imbalance since late childhood, with good response to acetazolamide, before developing moderate chronic cerebellar ataxia. Brain MRI showed cerebellar atrophy, especially in the vermis, in both patients. Direct sequencing of CACNA1A identified a heterozygous 1360G>A mutation in exon 11 resulting in the substitution of alanine for threonine at residue 454 (p.Ala454Thr). This is the first description of a change residing in the cytoplasmic I–II loop associated with a clinical phenotype.

黒毛和種子牛に発生した遺伝性内水頭症の染色体領域の解明

Congenital internal hydrocephalus (CIHY), characterized by cranial doming, paresis and ataxia at birth, has been occurring in Japanese Black calves in Tohoku area since 1988. The sires of the affected calves were of the same pedigrees. Embryo transfer was used to investigate the causative genes by producing several calves from a cow that delivered a calf with CIHY. The cow was superovulated by FSH and inseminated with the frozen semen of the suspected bull. Ultimately, ten calves were birthed from the recipient cows, with five showing symptoms of hydrocephalus. Clinically, four of the affected calves showed paresis, cranial doming and strabissumus. One calf showed a chronic convulsion and ataxia at 29 days and died. The pathological finding noted bilateral enlarged ventricles with an increase in cerebrospinal fluid. Gene scanning was performed with microsatelite markers using tissues and blood from five of the affected calves and five full-sib calves and the splenic tissues of eighteen half-sib calves that were embedded in paraffine for pathological study. The suspected gene was found near the centromere of chromosome 3 (BTA3). Using DNA markers, the common region of CIHY was found to be between MB101 and DIK069. The pidemiological findings clarified this CIHY as a single autosomal recessive disease.

A possible variant of neuro-Behçet disease presenting chronic progressive ataxia without mucocutaneo-ocular symptoms

Behçet disease (BD) is a chronic relapsing multisystem disorder of unknown etiology, which preferentially affects the oral and genital mucous membranes, skin, and eyes. Neurological involvement is one of the most serious manifestations of BD, known as neuro-Behçet disease (NBD). We here describe clinical, radiological, and neuropathological findings for two patients with a possible variant of NBD, who manifested progressive ataxia in the absence of mucocutaneo-ocular signs characteristic for BD. Both patients presented a slowly progressive cerebellar phenotype, accompanied by behavioral changes and sphincter disturbance. Brain MRI scan revealed mild atrophy in pons and cerebellum. Both patients showed a mild CSF pleocytosis, and were positive for HLA-B51. The post-mortem examination performed in one patient, showed widespread foci of chronic encephalitis, consistent with the diagnosis of NBD. Steroid pulse therapy was effective in one patient. Identifying the progressive ataxia phenotype of NBD without mucocutaneo-ocular symptoms is important, because these patients may benefit from early steroid therapy.

Ataxie avec sensibilité au gluten, mythe ou réalité ?

Gluten ataxia refers to the association of idiopathic ataxia despite exhaustive investigations with gluten sensitivity defined by anti-gliadin antibodies (AGA) presence in blood. This is a controversial concept. We screened 33 patients, who were hospitalized in 2003 and had subacute or chronic ataxia for presence of circulating AGA. Twelve patients were positive and their clinical and biological features were studied. Among the twelve patients, we concluded that gluten ataxia was present in only eight, including one case of celiac disease. Among these eight patients, five had the usual features of gluten ataxia (progressive cerebellar ataxia affecting mainly lower limbs), but one patient presented unusual left cerebellar hemisyndrome and the two others displayed polyneuropathy with proprioceptive ataxia. Cerebellar atrophy was confirmed with magnetic resonance imaging in five cases and association with other antibodies was found in six cases. Among the four other patients positive for AGA, investigations revealed one case of multiple sclerosis, one case of late-onset Friedreich ataxia, one case of basilar tuberculous meningitis and one case of type 2 diabetes. Screening for AGA presence should be systematically performed at presentation of patients with unknown etiology ataxia; in the event AGA are present without any other etiology, treatment with gluten-free diet must be discussed. However, the responsibility of AGA in the pathogenesis of neurological signs is highly debatable and further experimental work is required. Two pathophysiological hypotheses are suggested: (1) overexpression of cerebellar epitopes, in case of primary cerebellar pathology, leading to excessive immune response directed against these epitopes; and (2) molecular mimicry with cross-reactivity of antigens usually directed against gliadin, but also recognizing Purkinje cells epitopes.