A case of Machado-Joseph disease presenting pure cerebellar ataxia]

We report a 61-year-old woman with Machado-Joseph disease (MJD) presenting with pure cerebellar ataxia. The patient exhibited an unsteady gait at the age of 51 years. She was admitted to our hospital at the age of 61 years. Her older brother had been diagnosed as having spinocerebellar degeneration (SCD). Our patient showed gaze-evoked nystagmus, wide-based gait, slight lack of coordination of the four extremities, mildly ataxic speech and slight decrease in the bilateral Achilles tendon reflexes. Babinski's sign was absent. Sensory impairments were not present and muscle tone and muscle strength were normal. There was no autonomic dysfunctions. MRI revealed moderate atrophy of the cerebellum and pons. We performed gene analysis of SCD using white blood cells from the patient, and the analysis showed 70 CAG repeats in the MJD1 gene, which is an abnormally high number of repeats. Compared with three reported cases of MJD presenting pure cerebellar ataxia, only our patient showed a nasal voice. The number of CAG repeats in the MJD1 gene of our patients was the most prolonged of the four cases. MJD should be considered in patients with familial SCD even if their neurological signs and symptoms outside the cerebellum are not obvious.     

A steroid-effective case with "prolonged" cerebellar ataxia]

We reported a girl with "prolonged" cerebellar ataxia for whom steroid was effective. At the age of 9 months, she developed gait disturbance, tremor and abnormal eye movements following exanthema subitum. Her symptoms were prolonged for more than 4 months and she was admitted to our hospital. The symptoms were successfully suppressed with repeated ACTH treatment but recurred in a few weeks after cessation of the therapy. Steroid was also effective but reduction of the dosage resulted in worsening of symptoms. Immunological mechanism was suspected for her disorder because of her response to steroid and ACTH.     

A case of midbrain infarction with acute bilateral cerebellar ataxia]

An 81-year-old man was suffered from acute dysarthria and gait disturbance. Bilateral cerebellar ataxia and ataxic dysarthria were the only neurological findings. MRI images revealed an infarction in the lower and medial part of the midbrain. We consider that bilateral ataxia of the present case was caused by the lesion at the decussation of the superior cerebellar peduncle.     

A case with posterior column ataxia associated with cerebellar ataxia and sensory neuropathy]

The patient was a 72-year-old man who had a history of subtotal gastrectomy for gastric ulcer at age of 37 years. He had no familial history of hereditary disorders. In 1980 he noticed mild ataxic gait which exaggerated while he closed eyes. The symptoms increased gradually, and four years later he noticed hypoesthesia of his soles. In 1983 he was admitted to the National Center Hospital for Mental, Nervous and Muscular Disorders for the first time. Neurological examination revealed dysarthria, ataxic gait, disturbance of coordination to a slight degree, and muscle strength of the upper and lower limbs were in normal range. Mild hypoesthesia of pain and temperature sensation, and marked decrease of deep sensation and vibration of the lower extremities were demonstrated. Romberg sign was positive. EMG studies revealed low amplitude of action potential and normal motor nerve conduction velocity. Biopsy of the sural nerve showed marked decrease of both large and small myelinated fibers. In 1998 he was admitted second time for the further examination. Laboratory examination including routine blood examination, blood chemistry including CRP, TPHA, vitamin B1, B2, B12, A, E, K, hexosaminidase A in leucocyte were in normal range. CSF was normal. Genetic studies including SCA 1, 2, 3, 6, DRPLA, CMT1A, CMTX 1 were all negative. MCV of lower limbs was in normal range, though SCV was not evoked in the upper and lower limbs. MRI studies showed mild atrophy of the bilateral lobulus of the cerebellum which was not so much changed in the last 5 years. The clinical symptoms revealed dominant posterior column disturbance, ataxia and sensory neuropathy. These combination was not described in the previous literature, and this case may be a new variant of the spinocerebellar degeneration.     

A case of aceruloplasminemia presenting as cerebellar ataxia with homozygous mutation nt2602 delG]

Aceruloplasminemia is an autosomal recessive disorder of iron metabolism caused by mutations in the ceruloplasmin (Cp) gene. We reported the results of clinical and molecular studies on a Japanese family with aceruloplasminemia. A 58-year-old man who had had diabetes mellitus for more than 30 years developed cerebellar ataxia several years before. He was found to have mild retinal degeneration too. Laboratory findings revealed a complete deficiency of serum ferroxidase activity and undetectable serum Cp. Magnetic resonance imaging showed a pronounced hypointensity in the bilateral putamina, caudate, thalamus and dentate nuclei on both T1- and T2-weighted images suggesting the presence of iron overload. We identified a homozygous deletion mutation (nt2602 delG) of the Cp gene in the patient, and the same heterozygous mutation in his unaffected father. To date, at least 29 mutations in the Cp gene have been identified. Although an individual with a heterozygous mutation has been believed to be an asymptomatic carrier like his father, some patients with such a condition were recently described to show neurological deficits. The variation in clinical findings may be explained partly by the difference in the severity of generation of free radicals caused by iron deposition or the environmental factors such as aging. Further investigations would be required to elucidate the molecular mechanisms of this late onset neurodegeneraion.     

An autopsied case of progressive supranuclear palsy presenting with cerebellar ataxia and severe cerebellar involvement

A Japanese male patient presented with gait disturbance at the age of 69 years. His principal symptom was cerebellar ataxia for several years. He was initially diagnosed as having olivopontocerebellar atrophy because dysarthria and ataxia gradually developed, and head CT scan showed apparent atrophy of the cerebellum and brainstem and dilatation of the fourth ventricle. Later, he showed vertical gaze palsy, dysphagia, retrocollis, parkinsonism, axial dominant rigidity and grasp reflex, and therefore, the diagnosis was modified to progressive supranuclear palsy (PSP). Progressive atrophy of the frontotemporal lobe, cerebellum and brainstem, and dilatation of the lateral, third and fourth ventricles were evident on MRI. Gastrostomy and tracheotomy were performed 9 and 10 years after onset, respectively, and the patient died after 11 years disease duration. At autopsy the brain weighed 1000 g and showed atrophy of the frontotemporal lobe, cerebellum and brainstem. Neurofibrillary tangles, mainly globose‐type revealed by Gallyas‐Braak silver staining, were extensively observed in the cerebral cortex and subcortical grey matter. Numerous glial fibrillary tangles, including tuft‐shaped astrocytes and coiled bodies, and extensive argyrophilic threads were also recognized, particularly in the frontal lobe, basal ganglia, cerebellar white matter, brainstem and spinal cord. The Purkinje cell layer showed severe neuron loss with Bergmann's gliosis, and the dentate nucleus showed severe neuron loss with grumose degeneration. Tau‐positive/Gallyas‐positive inclusions in the Purkinje cells and the glial cells of the Purkinje cell layer were observed. Pathological findings of the present patient were consistent with the diagnosis of PSP, but the olivopontocerebellar involvement, particularly in the cerebellum, was generally more severe, and the quantity of tau‐positive/Gallyas‐positive structures were more abundant than in typical PSP cases. The existence of a distinct, rare PSP subtype with severe olivopontocerebellar involvement, “PSP‐C“, which tends to be clinically misdiagnosed as spinocerebellar degeneration in the early disease stage, is noteworthy. The present case corresponded to this rare subtype of PSP.     

A case of cerebellar degeneration showing amaurosis fugax due to primary angle-closure glaucoma]

We reported a 76-year-old woman with cerebellar degeneration who had transient monocular visual loss following the acute attacks of angle-closure glaucoma. The episodes occurred only at night approximately every ten days. She denied pain or any other associated symptoms. Ophthalmological examinations including intraorbital pressure, ocular fundus, visual acuity and visual field showed no abnormalities between the attacks. Provisional diagnosis on admission was amaurosis fugax from retinal embolization. After admission, she developed a typical acute attack of glaucoma accompanied by severe pain in her left eye. Intraorbital pressures were 12 mmHg in the right eye and 58 mmHg in the left, and the diagnosis of primary angle-closure glaucoma was made gonioscopically. Following peripheral iridotomy by laser therapy, her visual acuity recovered and episodes of visual loss disappeared. In this case, the attacks of glaucoma were unusually painless, so it is very difficult to distinguish between glaucoma and amqurosis fugax from retinal embolization. The transient visual loss always occurred at night, and retrospectively, this characteristic feature might indicate that these episodes were acute attacks of angle-closure glaucoma. Glaucoma is one of the diseases that can cause painless amaurosis fugax.     

A suspected case of alcoholic pellagra encephalopathy with marked response to niacin showing myoclonus and ataxia as chief complaints]

We report a 47-year-old alcoholic man with alcoholic pellagra encephalopathy (APE) showing myoclonus and ataxia as chief complaints. He had been a heavy drinker for 30 years. He had noticed appetite loss and subsequently showed a subacutely progressive gait disturbance. He had no history of diarrhea, dementia, or dermatitis. On admission, he showed severe alcoholic liver cirrhosis with a large amount of ascites, limbs and truncal ataxia, myoclonus of the limbs and areflexia, although his consciousness was alert and there were no sign of dermatitis. Though the plasma level of ammonia was normal, we started administration of amino acids suspecting hepatic encephalopathy. Symptoms showed no improvement, and subsequent administration of thiamine was also ineffective. A decreased serum level of niacin was demonstrated. After administration of nicotinamide, the symptoms improved gradually. This patient received a diagnosis of APE. Endemic pellagra, characterized by the classical triad of dermatitis, diarrhea and dementia, is known to be caused by a dietary deficiency of the niacin, and has now become very rare in developed countries. At present, pellagra is encountered most often in patients with chronic alcoholism, which is called APE. APE patients often show only disturbance of consciousness. Although several reports has described ataxia and myoclonus in patients with APE, APE patients with myoclonus and ataxia as chief complaints have not previously been reported. On autopsy cases, central chromatolysis of neurons in the dentate nucleus of the cerebellum, gracile and cuneate nuclei, and the Clarke's column has been demonstrated. The APE patients would show myoclonus and ataxia as their first symptoms. In conclusion, we would like to emphasize that administration of niacin should be started for the treatment of chronic alcoholic patients showing myoclonus and ataxia even without the classical triads found in endemic pellagra patients.     

A case of periodic ataxia]

We report a sporadic case of periodic ataxia characterized by recurrent attacks of vertigo and ataxia. A 62-year-old male was known to have nystagmus at the age of 18. He has had recurrent episodes of vertigo and ataxia since the age of 48. During an attack remarkable downbeat nystagmus, limb ataxia predominant in the lower extremities and ataxic gait were present. MRI demonstrated an atrophy of the anterosuperior region of the cerebellar vermis. Vertical nystagmus, dysesthesia of gloves and stocking type and deep sensory disorder persisted during interictal intervals. There is no finding which supports this case to be vascular disorder, congenital anomaly, tumor, infection or demyelinating disease. We thought this case to be periodic ataxia and to belong to vestibulocerebellar ataxia reported by Farmer and his colleagues.     

A case of idiopathic torsion dystonia showing blepharospasm at the onset

We report a 12-year-old boy with idiopathic torsion dystonia. Blepharospasm appeared at the age of 10, followed by truncal hypertonia and progressive scoliosis after 1 year. He had bizarre involuntary movement of his limbs upon waking, which was initially misinterpreted as a psychogenic reaction. Routine neurological examinations revealed no abnormality. Treatment with diazepam, bacrophen, 1-dopa, and clonazepam, led to only short time improvement of symptoms. At the age of 14, his symptoms gradually improved in natural course. At present he is 15 years old, and capable of normal daily activities. His clinical course was not typical of idiopathic torsion dystonia and very rare in children.     

A case of spinocerebellar ataxia type 6 with hypochondriasis and severe parkinsonism]

We report a case of 68-year-old woman who was diagnosed spinocerebellar ataxia type 6 (SCA 6) by genomic testing. She presented hypochondriasis, parkinsonism, and ataxia. Since the age of 60, she noted difficulty in walking due to dizziness, and MRI showed minimal cerebellar atrophy. She became unable to walk without assistance at the age 67. She was referred to us when she was 68 years old. She had no family history of cerebellar ataxia, and her general physical examination was normal. Her speech was fluent, with neither slurring nor scanning, and she complained of much anxiety regarding her physical condition and was diagnosed as having hypochondriasis. Neurological examination revealed parkinsonism consisting of small steppage gait, mask-like face, akinesia, rigidity of neck and limbs, and postural instability. She also showed cerebellar signs such as saccadic smooth pursuit, ataxia of upper and lower limbs, and increased tendon reflexes. Her parkinsonism had developed slowly and symmetrically yet she showed a lack of response to levodopa. Our results suggest that the genomic testing is useful for differential diagnosis for the diseases presenting ataxia and parkinsonism, even if the family history is negative.     

A case of transient isoniazid-induced myoclonic seizures]

We report a unique patient who had temporary isoniazid-induced myoclonic seizures. A 74-year-old man noticed involuntary movements in the upper extremities when he received isoniazid in pulmonary atypical mycobacteriosis late June 1996. Neurological examination revealed myoclonic jerking in the upper limbs. Although isoniazid treatment had been given to November 1996, the myoclonic seizures were spontaneously ameliorated at 2 weeks following the onset. The second administration of isoniazid was started for the exacerbation of pulmonary atypical mycobacteriosis in February 13, 1999. Immediately he developed myoclonic seizures in the upper extremities. Neurological examination showed myoclonic jerking in the upper extremities and cerebellar ataxia in the lower extremities. These neurological deficits were naturally improved within a week. Brain MRI suggested multiple lacunar infarction. EEG showed slow theta and sharp waves. Somatosensory evoked potential (SEP) revealed giant potentials. There was no renal or liver dysfunction. Serum vitamin B6 levels were decreased slightly. The metabolic studies of serum and cerebrospinal fluid isoniazid concentrations demonstrated slow inactivation of this agent. After the end of isoniazid treatment, EEG and SEP were normal. The results of these studies indicated that slow inactivator of isoniazid and its epileptogenic effects might contribute to the pathogenesis of myoclonic seizures in our patient.     

A case of acute cerebellar ataxia with an MRI abnormality

A 5-year-old boy with acute cerebellar ataxia was examined by means of magnetic resonance imaging (MRI) and was found to have a lesion showing low and high signal intensity in T1- and T2-weighted images, respectively, in the left cerebellar peduncle in the acute phase. The lesion disappeared in the convalescent phase.     

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 delta2 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.     

A case of adult-onset Huntington disease presenting with spasticity and cerebellar ataxia, mimicking spinocerebellar degeneration]

We report an adult-onset case of Huntington disease presenting with spasticity and cerebellar ataxia. The patient, a 47-year old woman, was admitted to our clinic because of progressive involuntary movements. Her elder brother suffered from the similar symptoms. Neurologically, she had quick temper, dementia, generalized chorea, spasticity and truncal ataxia. MRI demonstrated atrophy of caudate, midbrain, pons and cerebellum. From these clinical and MRI findings, she was suspected to have a form of spinocerebellar degeneration (SCD), particularly DRPLA. However, DNA analysis showed CAG repeats in huntington gene was expanded (47/20). Accordingly she was diagnosed as having adult-onset Huntington disease, mimicking SCD. This case indicates Huntington disease may present atypical clinical features and it is crucial to determine CAG repeat size in huntington gene for the patient with dementia and/or movement disorders, etiology of which is unknown. The relationships between clinical phenotypic variations and huntington gene expression are not determined.     

A case of early onset cerebellar ataxia with hearing loss, mental disturbance and primary hypogonadism]

A 14-year-old girl, whose birth and developmental history were normal till the age of 7, was admitted to our hospital because of slowly progressive difficulties in walking, speaking and hearing. She also complained of absence of menstruation. She showed poor school records since the age of 7. On neurological examination, she showed limb and truncal ataxia. There was no nystagmus but slurred speech was found. Muscular power was good and her sensory system was normal. Tendon reflexes were equally present, and plantar reflexes were flexor. Bilateral moderate nerve deafness was also present. Mental deficiency was diagnosed on an intelligence test. Brain CT and MRI showed cerebellar atrophy. Gynecological examination revealed scanty pubic hair and small uterus. Karyotype was 46XX. Endocrinological studies demonstrated high level of FSH, low level of E2, and the normal response to pituitary stimulation with LHRH, indicating the existence of primary hypogonadism. Although the etiology of this multisystem disorder is unknown, it is possible that both nervous and endocrine disorders were genetically determined.