Spinocerebellar ataxia type 10 (SCA10) is a dominantly inherited neurodegenerative disease caused by expansion of the ATTCT pentanucleotide repeat in intron 9 of a novel gene, ATXN10, on chromosome 22q13.3. It is clinically characterized by progressive ataxia, seizures, and anticipation, which can vary within and between families. The length of the expanded ATTCT repeats is highly unstable on paternal transmission and shows a variable degree of somatic and germline instabilty, revealing complex SCA10 genetic mechanisms. Moreover, the purity of the expanded repeat element may be a disease modifier. ATTCT repeats have been recently shown to form unpaired DNA structure and may serve as an aberrant DNA replication origin, potentially contributing to repeat instability and cell death. How this untranslated ATTCT expansion leads to neurodegeneration has been still controversial. We discuss several possible pathogenic mechanisms for SCA10, and growing number of evidence indicates a gain-of-function RNA mechanism, similar to the myotonic dystrophies caused by non-coding CTG or CCTG repeat expansions.

View full abstract

[¹²³I] Meta-iodobenzylguanidine (MIBG) myocardial scintigraphy has been used to evaluate postganglionic cardiac sympathetic innervation in heart diseases and some neurological disorders. To see clinical usefulness of MIBG myocardial scintigraphy to differentiate Parkinson's disease (PD) and dementia with Lewy bodies (DLB) from related movement disorders and Alzheimer disease (AD), we performed MIBG myocardial scintigraphy in patients with these disorders. Cardiac uptake of MIBG is specifically reduced in PD and DLB, and this imaging approach is a sensitive diagnostic tool that possibly differentiates PD and DLB from related movement disorders and AD.
To see pathological basis of the reduced cardiac uptake of MIBG in Lewy body disease, we immunohistichemically examined cardiac tissues from patients with PD, DLB, related movement disorders and AD using antibodies against tyrosine hydroxylase (TH) and phosphorylated neurofilament (NF). Not only TH- but also NF-immunoreactive (ir) axons in the epicardial nerve fascicles were markedly decreased in Lewy body disease, namely cardiac sympathetic denervation, which accounts for the reduced cardiac uptake of MIBG in Lewy body disease. Patients with PD and DLB have Lewy bodies (LBs) in the nervous system, whereas patients with multiple system atrophy (MSA), progressive supranuclear palsy, corticobasal degeneration, parkin-associated PD and AD have no LBs in the nervous system. Even in patients with MSA, cardiac sympathetic denervation was associated with the presence of LBs. Therefore, cardiac sympathetic denervation is closely related to the presence of LBs in a wide range of neurodegenerative processes. Taken together, we conclude that the reduced cardiac uptake of MIBG is a potential biomarker for the presence of LBs.
Because α-synuclein is one of the key molecules in the pathogenesis of PD, we further investigate how α-synuclein aggregates are involved in degeneration of the cardiac sympathetic nerve in PD. We immunohistochemically examined cardiac tissues from patients with incidental Lewy body disease (ILBD) and PD using antibodies against TH and phosphorylated α-synuclein. We found that (1) α-synuclein aggregates in the epicardial nerve fascicles, namely the distal axons of the cardiac sympathetic nerve, were much more abundant in ILBD with preserved TH-ir axons than in ILBD with decreased TH-ir axons and PD; (2) α-synuclein aggregates in the epicardial nerve fascicles were closely related to the disappearance of TH-ir axons; (3) in ILBD with preserved TH-ir axons, α-synuclein aggregates were consistently more abundant in the epicardial nerve fascicles than in the paravertebral sympathetic ganglia (pSG); and (4) this distal-dominant accumulation of α-synuclein aggregates was reversed in ILBD with decreased TH-ir axons and PD, which both showed decreased or depleted TH-ir axons but more abundant α-synuclein aggregates in the pSG. These findings indicate that accumulation of α-synuclein aggregates in the distal axons of the cardiac sympathetic nervous system precedes that of neuronal somata or neurites in the pSG and that heralds centripetal degeneration of the cardiac sympathetic nerve in PD. This chronological and dynamic relationship between α-synuclein aggregates and distal-dominant degeneration of the cardiac sympathetic nervous system may represent the pathological mechanism underlying a common degenerative process in PD.

View full abstract

We report a patient of a 20-year-old woman of Takayasu's arteritis and hypertensive encephalopathy. The symptoms started with headache and vomiting following status epilepticus. On arrival at the emergency room in our hospital, fever was apparent and cerebrospinal fluid examination revealed pleocytosis. After the admission, the patient presented with hypertension, decreased right brachial pulse and the difference between bilateral brachial arterial blood pressures on examination. There had been no history of arterial hypertension. The MR angiography revealed stenoses of the bilateral cervical, especially right cervical, right middle cerebral and left renal arteries. Brain MRI showed transient hyperintense lesions of the left fronto-parieto-occipital cortices and subcortical white matter in FLAIR and diffusion weighted images. These alterations suggested the presence of reversible vasogenic edema induced by hypertensive encephalopathy. We need to be aware of young patients with convulsion, especially young women, who has arterial hypertension as well as the difference with blood pressures between extremities.

View full abstract

We report a 49-year-old man who was a human T-cell leukemia virus type 1 (HTLV-1) carrier, born in Okinawa prefecture where both strongyloidiasis and HTLV-1 are endemic. He presented with fever, headache and urinary retention. On the basis of CSF examination and MRI findings, his condition was diagnosed as myelitis. He received methylprednisolone pulse therapy. He was transferred to our hospital due to severe paralytic ileus. Strongyloides stercoralis (S. stercoralis) was found in the duodenal stained tissue of a biopsy specimen. Ivermectin applied both orally and through enema were ineffective because of severe ileus and intestinal bleeding. Nine mg (200μg/kg) of ivermectin solution was administered subcutaneously every other day for five days (total amount 45mg). The S. stercoralis burden in the stool decreased and paralytic ileus gradually resolved. Three weeks after the resolution of S. stercoralis infection, purulent meningitis developed and acute obstructive hydrocephalus appeared. The hydrocephalus improved by ventricular drainage. Approximately three months after drainage, he died of incidental aspiratory pneumonia. Autopsy showed neither eggs nor larvae of S. stercoralis in the organs. In this case, the fourth reported case in the world, subcutaneous ivermectin injection was dramatically effective. We should consider a diagnosis of strongyloidiasis for any patient from Okinawa prefecture who was an HTLV-1 carrier presenting with unknown origin ileus after treatment of steroid therapy.

View full abstract

We report a 72-year-old man with eosinophilic myositis (EM). At age 71 he noticed a painful nodule in his left calf. A biopsy (first biopsy) showed marked infiltration of mononucleated cells and necrotic muscle fibers. Several phagocytosed fibers were also seen. He was diagnosed as having myositis. The painful nodule disappeared spontaneously. At age 72, he again had a painful nodule, but this time in his right calf; again, this disappeared spontaneously on the first admission. Just after discharge, he noted painful nodules in the left thigh and right anterior tibial muscles and was again admitted (second admission). Neurological examination revealed mild proximal-dominant weakness in all four extremities but no other abnormalities. Laboratory studies showed elevated creatine kinase (CK) level (38,803U/l; normal 62-287) and positive Jo-1 antibody, but no eosinophilia. Needle electromyography of the limb muscles showed myogenic patterns. Magnetic resonance imaging of the lower limbs demonstrated several T2-high and gadolinium (Gd)-enhanced lesions. Muscle biopsy (second biopsy) from the left quadriceps femoris showed marked infiltration of eosinophils; he was diagnosed as having EM. Administration of prednisolone was initiated at 60 mg/day and then gradually tapered. After starting treatment with steroids, his muscle weakness gradually ameliorated, CK level dramatically decreased, and the nodules disappeared. Clinically, the patient had developed localized nodular myositis (LNM), but pathologically it was EM without peripheral blood eosinophilia and positive Jo-1 antibody that is occasionally found in polymyositis (PM). Thus, this patient demonstrated overlapping characteristics of EM, LNM, and possibly PM, suggesting that a common mechanism underlay these conditions. As discussed, the involvement of eosinophils in three inflammatory myopathies was indicated.

View full abstract

We report herein a patient of poststroke dementia (PSD) following left medial occipitoparietal hemorrhage triggered by drainage of an acute traumatic subdural hematoma. The patient, an independent 73-year-old man, became dependent due to dementia. Cognitive dysfunction was characterized by moderately decreased IQ, severe memory disturbances, topographical disorientation, executive dysfunction and loss of self-awareness. Cognitive dysfunction has not advanced for 3 years. Hypo-perfusion in the whole brain, particularly in the left temporal and parietal regions, was visible on ¹²³I-IMP SPECT images. Magnetic resonance imaging demonstrated damage to the left posterior cingulate cortex, cingulate bundle, superior parietal lobule and subcortical region of the occipital lobe. The fornix was spared. Some subcortical small spotted lesions were detected, but periventricular lucency was not prominent. Structures known to be important in memory but spared by the lesion included the thalamus and basal forebrain. Small spotted subcortical lesions were detected in bilateral hippocampi, which are also known to be important in memory, but these were probably silent lesions. This case suggested that dementia is brought on by the lesion of the left posterior cingulate bundle and retrosplenial cortex causing amnesia by disrupting the cingulate-hippocampal connection or the retrosplenial cortex itself, with the lesion of the left occipitoparietal subcortex causing frontal dysfunction by disrupting the dorsal limbic pathway and occipitofrontal fasciculus of the prefrontal circuits.

View full abstract

A 56-year-old right-handed man with recurrent orogenital aphtoid ulcers and bilateral uveitis had presented with memory disturbance, dressing apraxia and constructional apraxia at age 53. Neuro-Behçet disease was diagnosed based on pathergy test results and positivity for HLA-B51. Four months after azathioprine was introduced, he presented with subacute spastic paraparesis and urinary retention at age 56. Neurological examination demonstrated hyperreflexia in the lower limbs without pathological reflexes. He also showed memory disturbance, dressing apraxia and constructional apraxia. Spinal cord MRI showed a longitudinally extensive spinal cord lesion (LESCL) from C1 to Th3 with partial gadolinium enhancement from C6 to C8. Brain MRI showed moderate atrophy of the right temporal and parietal lobes without contrast enhanced lesion. There were hyperintense lesions in the pons, bilateral periventricular white matter and right parietal subcortical white matter. Cerebrospinal fluid analysis showed mild lymphocytic pleocytosis. After intravenous methylprednisolone treatment, clinical symptoms largely resolved and the abnormal intensities with contrast enhancement of the cord disappeared. However, higher cortical dysfunctions were not changed. LESCL may reflect inflammatory venous vasculitis with edema extending along the neural fibers since the lesion shows excellent responses to steroid without neurological sequelae. Differential diagnosis of neurological diseases demonstrating LESCL should include Neuro-Behçet disease.

View full abstract

We report here an 83-year-old woman presenting with somnolence possibly induced by indapamide. She was diagnosed as having hypertension (180/110mmHg), and 1mg/day of indapamide was administered starting in October, 2002. Two months later, she complained of nausea, vomiting, and appetite loss and frequently fell down. On admission, she was hypotensive (90/54mmHg). Neurologically, she was in a somnolent state (Japan Coma Scale 2-20), and showed brisk deep tendon reflexes of both upper limbs with bilateral Chaddock signs. Laboratory examination showed severe hyponatremia(115mEq/l) and hypokalaemia (2.8mEq/l). On brain MR imaging, there were no remarkable abnormalities, except for multiple lacunar infarctions. After the administration of indapamide was discontinued, her consciousness level and serum electrolytes immediately returned to normal levels. After a good effect for stroke prevention was reported, indapamide was widely prescribed in combination with angiotensin-converting enzyme (ACE) inhibitors, or angiotensin II receptor blocker (ARB) among the neurologists. We should keep in mind the risk of hyponatremia and hypokalaemia occurring in patients receiving indapamide, especially elderly women.

View full abstract

We investigated the correlation between results of ¹²³I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy and those of cardiovascular autonomic function tests in patients with Parkinson's disease (PD). ¹²³I-MIBG myocardial scintigraphy and a 5-minute standing test were performed in 50 patients with PD and in 19 control subjects. The value of the basal plasma noradrenaline (NA) level was used as an index of basal sympathetic nerve activity, and %NA was used to assess the response of sympathetic nerve activity. In addition, the parameters of Δ BP and Δ HR were evaluated to assess the autonomic response of the cardiovascular system. A mild, but significant correlation was observed between the myocardium to mediastinum (H/M) ratio and the values of the plasma NA baseline (r=0.35, p<0.05 in early image, r=0.29, p<0.05 in delay image). No significant correlation was observed between the H/M ratio and the other parameters (%NA, Δ BP, Δ HR). These results suggest that ¹²³I-MIBG myocardial scintigraphy may be associated with the basal sympathetic nerve activity, but not with autonomic nervous response of the cardiovascular system in patients with PD.

View full abstract

We report a 43-year-old woman with familial amyotrophic lateral sclerosis (FALS) who died of massive bleeding from a tracheoarterial fistula. Four years after the onset of the disease, she received invasive ventilation by tracheostomy because of respiratory failure. Four years and 7 months later, she showed an abrupt hemorrhage from the tracheostomy and died. The postmortem examination revealed a fistulous tract between the tracheal mucosal ulcer and the brachiocephalic trunk. The ulcer was in close proximity to the tracheostomy tube. In order to avoid such unexpected complications, we should observe the contact site between the tracheal mucosa and the tracheal tube in chronic tracheostomy patients.

View full abstract