Identification of causative genes for hereditary dystonia and elucidation of their functions are crucial for better understanding of dystonia pathogenesis. As seen in other hereditary neurologic disorders, intra- and inter-familial clinical variations have been demonstrated in hereditary dystonia. Asymptomatic carriers can be found due to alterations in penetrance, generally reduced in succeeding generations. Current known dystonia genes include those related to dopamine metabolism, transcription factor, cytoskeleton, transport of glucose and sodium ion, etc. It has been reported that effects of deep brain stimulation can vary significantly depending on genotype. Accumulation of genotype-outcome correlations would contribute to treatment decisions for dystonia patients.

View full abstract

Dropped head syndrome is seen in various diseases. We investigated its pathophysiological mechanisms with physical and radiological examination, surface EMG and responses to physiotherapy. Subjects had dropped head as a complaint, but their primary diagnoses were various. We investigated 16 cases: 5 cases of Parkinson disease, 5 cases of multiple system atrophy predominant parkinsonism, 3 cases of cervical spondylosis and 3 cases with other diagnoses. We found that patients had common findings such as bulging of cervical muscles, and tonic EMG activities mainly in the extensors in the sitting and standing position, but in the flexors of the neck only in the supine position. Of the 16 cases, 14 were treated with physiotherapy to improve the alignment of the pelvis and whole vertebral column; 6 of the 14 cases (63%) showed remarkable improvement. We conclude that the primary reason of dropped head syndrome is unknown in Parkinson disease and cervical spondylosis, but also that many of the patients have secondary changes in alignment of the skeletomuscular system which could be treated with physiotherapy.

View full abstract

Fibromuscular dysplasia (FMD) is a non-atherosclerotic, non-inflammatory arterial disease of unknown etiology. We report a 26-year-old woman who presented with transient ischemic attack (TIA) due to bilateral internal carotid artery (ICA) occlusion and severe basilar artery stenosis, as FMD was diagnosed by a biopsy specimen of right ICA. Imaging investigations included magnetic resonance angiography and catheter angiogram without characteristic “string of beads" pattern, before reaching a definitive diagnosis by pathologist. Anti-platelet therapy and bypass surgery of superficial temporal artery-middle cerebral artery revealed no more clinical symptoms. This case of intra- and extra-cranial FMD gives a consideration of such rare disease in the differential diagnosis of TIA or stroke in healthy young patients. The literature of FMD is reviewed including pathological findings.

View full abstract

The patient was a 35-year-old female with an 9-year history of chronic kidney disease awaiting renal transplantation. She was brought to hospital by ambulance due to a generalized convulsive seizure. Her consciousness remained disturbed after treatment for her seizure, and sensorineural deafness was noted. Lactic acid and pyruvic acid levels were extremely elevated in both the plasma and the cerebrospinal fluid, and brain atrophy was obvious on brain imaging. These findings suggested mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes, which was confirmed by muscle biopsy. Previous renal biopsy specimen showed focal segmental glomerulosclerosis and granular swollen epithelial cells. She had no acute progression of the stroke-like episode with L-arginine treatment. However, the brain lesions expanded on MRI. Mitochondrial DNA analysis from a muscle biopsy specimen showed G13513A mutation. The G13513A mutation and the long history of preceding renal failure before the stroke-like episodes were distinctive features in this case.

View full abstract

A 46-year-old man with a history of the left retinal central artery obstruction and old cerebral infarction in the right middle cerebral artery region presented with right total blindness due to the right retinal central artery occlusion accompanied by a cherry red spot. He had been found to have a giant, 17 mm-in-diameter aneurysm of the right internal carotid artery and a right vertebral arterial aneurysm. The intra-arterial thrombolysis was performed with urokinase injection for the right eye artery origin, and the right eyesight has improved. Cranial and pelvic angiography showed multiple stenosis and dilatation of external carotid and internal iliac arteries. The right superficial temporal artery biopsy revealed the arteritis with fibrinoid necrosis. He was diagnosed as having polyarteritis nodosa (PAN) by clinical course, angiography, and the superficial temporal artery biopsy. Several studies have reported that PAN had less intracranial aneurysm and the diameter of the aneurysm was less than 5 mm. Our case is the first report that PAN had giant aneurysm of 17 mm, diagnosed by temporal artery biopsy. The temporal artery biopsy should be considered to diagnose PAN.

View full abstract

Inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD) is caused by mutations in the valosin-containing protein (VCP) gene. Varied clinical features caused by VCP mutations have been reported: these clinical phenotypes include distal myopathy, frontotemporal dementia and amyotrophic lateral sclerosis. We report a 49-year-old woman with 3-year history of progressive proximal limb muscle weakness. Family history was notable for her father with motor neuron disease and an elder brother with a myopathy involving tibialis anterior and quadriceps. Neurological examinations showed proximal muscle atrophy, especially severe atrophy of paravertebral muscles, right-dominant scapular winging, bilateral pyramidal signs and hyperreflexia. Serum CK level was normal and EMG showed chronic neurogenic changes. Muscle imaging (CT) showed adipose tissue replacement of paravertebral muscles and right serratus anterior, and marked atrophy of bilateral trapezius and vastus intermedius muscles. Her lumbar spine X-ray showed an osteosclerotic change in the vertebral body, where an increased uptake of Tc99m was also observed in bone scintigraphy. Although brain MRI was normal, neuropsychological examination showed a mild attention deficit with cognitive impairment. A muscle biopsy specimen revealed scattered fibers with rimmed vacuoles. These findings prompted us to analyze a mutation in the VCP gene. Genomic sequencing of all exons of the gene showed a heterozygous missense mutation in exon 5 (c.1315G>C; p.Ala439Pro).

View full abstract

We report a 51-year-old man with myopathy and dementia probably caused by a novel mutation of the valosin-containing protein (VCP) gene, in the form of a p.Ala439Pro substitution. At 43 years old, he presented at least 2-year history of weakness of right ankle dorsiflexion. Findings from muscle biopsy suggested distal myopathy with rimmed vacuoles. However, no mutation in the GNE gene was identified. He complained of giving way of the knee, and muscle imaging study showed adipose tissue infiltration in the quadriceps. Ten years later, he was confined to a wheelchair and became reticent and antisocial with slightly impaired memory. A muscle CT revealed atrophy or replacement by adipose tissue in the muscles of neck, trunks and extremities muscles with laterality and variation of the degree. The magnetic resonance imaging of the brain showed bilateral frontal and temporal lobe atrophy with left dominance. Findings were compatible with inclusion body myopathy with Paget's disease of bone and frontotemporal dementia.

View full abstract

A 39-year-old man suffering from progressive dysarthria, gait disturbance, and sensorineural deafness for 2 years was admitted to our hospital. He scored 28 points on the mini-mental state examination. He had previously undergone surgery at 24 years and 39 years of age for a cerebellar tumor (pilocytic astrocytoma). Superficial siderosis (SS) was diagnosed based on bloody cerebrospinal fluid (CSF) and the findings of T₂*-weighted head MRI that revealed marginal hypointensity of the surface of the cerebellum, brainstem, and cerebral cortex. After intravenous infusion and the oral use of hemostatic drugs (carbazochrome, tranexamic acid), the CSF became watery clear and his condition improved. Hemostatic drug therapy should be considered for SS.

View full abstract

We report the case of a 40-year-old woman with Alexander disease. She experienced single seizure as 1-year-old, and became less active after that. Her academic records in elementary school were poor. However, she graduated from junior college and was later employed as a clerk for a short duration. Her parents, who lived with her noticed her apathy when she was 38, and gait disturbance soon after. At the age of 40, she was admitted to a hospital because of a fall and was referred to us. Brain magnetic resonance imaging (MRI) showed significant leukodystrophy with frontal predominance, and cervical MRI revealed mild cervical cord atrophy with dilated central canal. We performed genetic analysis and found the R79H variant of the gene encoding the glial fibrillary acidic protein. The patient was diagnosed with Alexander disease and suspedted juvenile-onset on the basis of the genetic analysis and MRI findings. Patients with juvenile Alexander disease have been previously reported to have variable survival, ranging from the early teens to the 20's and 30's. Our patient may suggest that natural history of this disease is more variable than previously thought.

View full abstract

A 39-year-old man was suffered from bacterial meningitis spread from sphenoid sinusitis. During the first several days of the hospitalization, his clinical and laboratory findings were improved by the antibiotics. But he developed impaired consciousness and paraparesis on the sixth hospital day. A CT scan of the brain revealed pneumocephalus with compression of frontal lobes and the widening of the interhemispheric space between the tips of the frontal lobes, which was known as “Mount Fuji sign". Tension pneumocephalus was diagnosed on the basis of the clinical symptoms and the characteristic CT findings. As the bacterial meningitis itself was improving, the surgical treatment was not performed, but the antibiotics therapy continued. He gradually recovered and discharged without any other complications. The mechanism of tension pneumocephalus could not be disclosed. However, it was speculated that tension pneumocephalus was formed due to combined conditions of following factors; the fistula formation between sphenoid sinus and subdural space, the reduced CSF pressure on lumbar puncture, and a ball-valve mechanism though the fistula. We would emphasize that “Mount Fuji sign"on CT or MRI was the important finding to diagnose tension pneumocephalus.

View full abstract

[in Japanese]

View full abstract