Chigusa Watanabe

Serial diffusion-weighted imaging in MELAS

Abstract Clinical features of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) resemble those of cerebral infarcts, but the pathogenesis of infarct-like lesions is not fully understood. To characterise these infarct-like lesions, we studied two patients with MELAS using diffusion-weighted (DWI) MRI before and after stroke-like episodes and measured the apparent diffusion coefficient (ADC) in the new infarct-like lesions. These gave high signal on DWI and had much higher ADC than normal-appearing regions. The ADC remained high even 30 days after a stroke-like episode then decreased in lesions, with or without abnormality as shown by conventional MRI. We speculate that early elevation of ADC in the acute or subacute phase reflects vasogenic rather than cytotoxic edema. The ADC of the lesions, which disappeared almost completely with clinical improvement, returned to normal levels, which may reflect tissue recovery without severe damage. To our knowledge, this is the first study of DWI in MELAS.

Decrease of neurons in the medullary arcuate nucleus of multiple system atrophy: quantitative comparison with Parkinson's disease and amyotrophic lateral sclerosis

The physiological functions of the medullary arcuate nucleus are supposed to be involved in autonomic cardioventilatory regulation, but neuropathological studies on neurodegenerative diseases have rarely reported about the arcuate nucleus. We quantitatively examined the neuronal density of the arcuate nucleus in patients with multiple system atrophy (MSA, n = 3), Parkinsons disease (PD, n = 3), amyotrophic lateral sclerosis (ALS, n = 2), and control subjects (n = 6), and statistically compared the findings in each group. Although the neuronal densities in PD and ALS patients were not different from that in the controls, MSA patients showed a marked depletion of neurons in the arcuate nucleus. The neuronal density (/mm2, mean +/- SEM) in the arcuate nucleus was 9.27 +/- 10.4 in MSA, and was significantly decreased (P < 0.05; Wilcoxon test), compared with that in control subjects (87.1 +/- 12.2). These results suggest that the lesioned arcuate nucleus is related to the pathogenesis of dysatonomia in MSA.

Slowly progressive L-DOPA nonresponsive pure akinesia due to nigropallidal degeneration: a clinicopathological case study

We report an autopsy case of a 51-year old man who showed slowly progressive pure akinesia: freezing phenomenon and festination during 21 years of illness without tremor, rigidity, upward gaze palsy, bradykinesia and dementia, which were not responded to L-DOPA clinically. Neuropathological findings revealed the circumscribed regions in the substantia nigra and middle portion of the internal globus pallidus (GPi), without neurofibrillary tangles, neuropil threads, and glial fibrillary tangles. So this case was clearly distinguished with progressive nuclear palsy and pallidonigroluisian atrophy. It was first reported to describe that L-DOPA nonresponsive pure akinesia can arise from nigopallidal atrophy.

A case of pandysautonomia with associated sensory ganglionopathy

Since Young et al 1described a patient with acute loss of sympathetic and parasympathetic functions in 1969, many similar cases have been reported as being acute idiopathic autonomic neuropathy.2 Apart from acute cholinergic neuropathy, there are four types of acute idiopathic autonomic neuropathy, classified according to somatic nerve involvement: acute pandysautonomia, which has minimal or no motor or sensory dysfunctions3;acute autonomic and sensory neuropathy in which sensation is seriously involved4-6; Guillain-Barre syndrome with prominent dysautonomia, manifesting autonomic and somatic motor dysfunctions; and acute autonomic sensory and motor neuropathy, characterised by prominent dysautonomia and severe motor and sensory impairment. Despite minimal or no sensory disturbance, reduction of myelinated fibres in biopsied sural nerve has been found in several cases with acute pandysautonomia.3However, the exact site of pathological involvement in the sensory system remains unknown, because postmortem examinations have seldom been performed. We report a case of acute pandysautonomia with no evidence of significant somatic nerve involvement, accompanied by dorsal root ganglionopathy shown by postmortem examinations. An 18 year old male student experienced low grade fever, vomiting, and tingling pain in the limbs on 26 February 1987. Orthostatic syncopy occurred three times on the next day. Difficulty in emptying the bladder, alternate diarrhoea and constipation, and lack of sweating over the whole body developed rapidly. He was admitted to the Third Department of Internal Medicine, Medical College of Oita on 24 April 1987. On physical examination, he weighed 46 kg, with a recent weight loss of 14 kg. Blood pressure was 108/78 mm Hg in the supine position and heart rate was 88/min. When changing from the supine to theupright position, he …

Numerous conglomerate inclusions in slowly progressive familial amyotrophic lateral sclerosis with posterior column involvement

A 59-year-old woman with slow progression of the loss of motor function and predominant lower motor manifestation during a 14-year period showed familial amyotrophic lateral sclerosis (fALS) with posterior column involvement, neuropathologically. Conglomerate inclusions (CIs) were observed in the remaining neurons in various areas, including the spinal anterior horn, posterior horn, Clarks column, accessory cuneate nucleus, tegmental reticular formation, motor nucleus of the trigeminal nerve, nucleus of the facial nerve, hypoglossal nucleus, medial nucleus of the thalamus, dentate nucleus, and motor cortex (Betz cells). Immunohistochemically, it was newly identified that the CIs showed marked immunoreactions with antibodies to phosphorylated and non-phosphorylated neurofilaments and to 64, 120, and 200 kD neurofilaments. The CIs were partially immunoreactive with the anti-ubiquitin antibody, although they reacted only weakly (or not at all) with anti-Cu/Zn superoxide dismutase (SOD1) antibody. Ultrastructurally, the CIs were comprised of neurofilaments. These data suggest that this case might have been different from an example of fALS with Ile 113 Thr mutation in the SOD1 gene.

Relationship between neuronal loss and tangle formation in neurons and oligodendroglia in progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a progressive degenerative disorder characterized by neuronal loss, gliosis and abnormal fibril formation of abnormally phosphorylated tau protein in neurons and glia cells, but the cause is not clear at present. For the purpose of clarifying the pathological significance of accumulation of tau protein in neurons and oligodendroglia in PSP, we morphologically classified neurofibrillary tangles (NFT) and coiled bodies (CB) in oligodendroglia in three PSP brains into four stages, using double staining for immunohistochemistry with AT8 antibody and modified Gallyas‐Braak (GB) staining. AT8‐positive neurons without abnormal fibril structure with GB staining were classified as stage I, AT8‐positive neurons containing a few fibril structures with GB staining were classified stage II, AT8‐positive neurons containing mature fibril structures were classified as stage III, and AT8 negative neurons containing abnormal fibril structures stained only with GB staining were classified as stage IV (ghost tangles). These stages were also assessed for CB. Then we counted the number of cells of each stage in various brain regions to investigate the relationship of NFT and CB with neuronal loss and gliosis. The results showed that there were very few stage IV NFT and CB, which reflect cell death, but that stage III NFT and CB were abundant. Moreover, CB were abundant in regions with severe neuronal loss. These results suggest that appearance of CB is closely associated with degenerative regions.

Pure autonomic failure with motor neuron disease: report of a clinical study and postmortem examination of a patient.

to islands of neurotoxicity.4 A contribution from the otherwise insignificant basal ganglia calcification to the extrapyramidal features in our patient is doubtful. The highest concentrations of lithium in the CNS are found in the white matter of the pons.4 At one stage, our patient was totally immobile except for eyeblinks and eye movements, with which she could communicate. A normal MRI ruled out central pontine myelinolysis. Could this state, therefore, be attributed to the high concentration of lithium in the pons? In conclusion, lithium neurotoxicity usually develops after chronic treatment. Permanent sequelae are rare but the occasional occurrence of acute and persistent neurological symptoms warrants a note of caution, especially when lithium is used in combination with antipsychotic drugs.5 Lithium, preferably intracellular (red blood cells) should be carefully monitored to avoid neurotoxicity. Rarely, neurological sequelae may develop even at therapeutic serum concentrations. Therefore, the need for keen clinical observation, in addition to routine drug monitoring, especially during combination treatment with antipsychotics, cannot be overemphasised. J MANI S V TANDEL P U SHAH Department ofNeurology D R KARNAD Department ofMedicine, KEM Hospital, Bombay, India

Movement-related cortical potentials in myotonic dystrophy

OBJECTIVE To investigate a possible deficit of the voluntary movement mechanism within the central nervous system (CNS) in patients with myotonic dystrophy (MyD). METHODS Movement-related cortical potentials preceding voluntary extension of the right middle and index fingers were studied in 9 patients with MyD and compared with those in 11 age-matched healthy subjects and 9 age-matched patients with other neuromuscular disorders (NMDs). RESULTS The amplitudes of Bereitschaftspotential was smaller in MyD patients than in age-matched controls and age-matched patients with other NMDs although there was no statistically significant difference. The amplitude of negative slope was significantly smaller in MyD patients than in age-matched controls and age-matched patients with other NMDs. Clinical findings such as age, disease duration, degree of motor impairment and cognitive function had no effect on the individual electrophysiological parameters. CONCLUSIONS The present results suggest that subclinical abnormalities exist in CNS function associated with motor preparation and execution, which is independent of muscle weakness.

Argyrophilic structures stimulate glial reactions in neurofibrillary tangles and senile plaques

Neurofibrillary tangles (NFT) and senile plaques (SP) contain various pathological structures, and the majority of these pathological structures are argyrophilic. To investigate the glial reactions of the argyrophilic substance, we performed immunohistochemistry for microglia or for astroglia after Gallyas-Braak staining, which is one of the most sensitive silver impregnation techniques detecting argyrophilic structures in NFT and SP. We found that extracellular argyrophilic structures in NFT and SP showed glial reactions, and we observed reactive microglia in the center of NFT and SP in contrast to astroglia, which were situated in the periphery. These findings suggest that the exposed argyrophilic components in the extracellular space stimulate both glial reactions, but that there is a striking difference in localization between microglia and astroglia.

Heterotopic neurons in congenital myotonic dystrophy with mental retardation

We studied heterotopic abnormalities of the brain and spinal cord of a 48‐year‐old mentally retarded man with congenital myotonic dystrophy. He presented with a 2‐year history of progressive muscular weakness in the trunk and he developed dyspnea on effort and orthopnea 4 months pro to death. He died of acute renal failure and severe congestive heart failure. The characteristic neuropathological finding was a number of heterotopic neurons in the cerebrum. In the molecular layer of the cerebral cortex, medium‐sized neurons, pyramid‐shaped large neurons, and horizontal cells were noted. Many neurons were also distributed sporadically in the subcortical white matter. In the spinal cord, abnormally situated neurons were present in be posterior and lateral columns near the gray matter. These findings suggest that intrauterine maturational disturbance occurs during the period of migration and organization of neurons in the brain and spinal cord.