Peripheral sympathetic dysfunction in patients with Parkinson's disease without autonomic failure is heart selective and disease specific. taki@med.kanazawa-u.ac.jp.

UNLABELLED: The study was undertaken to investigate by means of iodine-123-labelled metaiodobenzylguanidine (MIBG) scintigraphy the peripheral sympathetic function in patients with Parkinson's disease (PD) without autonomic failure and in patients with related neurodegenerative diseases with parkinsonism. Seventy patients (33 men and 37 women, mean age 63+/-9.7 years) with parkinsonism and ten control subjects underwent MIBG scintigraphy. Of these 70 patients, 41 were diagnosed as having idiopathic PD, 9 multiple system atrophy (MSA), 6 progressive supranuclear palsy (PSP) and 2 corticobasal degeneration (CBD); the remaining 12 were diagnosed as having neurodegenerative disease with parkinsonism (P-nism) that did not meet the diagnostic criteria of any specific disease. Cardiac planar and tomographic imaging studies and subsequent whole-body imaging were performed 20 min and 3 h after the injection of 111 MBq MIBG. The early MIBG heart to mediastinum (H/M) ratio in PD (1.61+/-0.29) was significantly lower than that in the control group (2.24+/-0.14, P<0.01), P-nism (2.15+/-0.31, P<0.01), MSA (2.08+/-0.31, P<0.05) and PSP (2.30+/-0.24, P<0.01). The delayed H/M ratio in PD (1.47+/-0.34) was also significantly lower than that in the control group (2.37+/-0.14, P<0.01), P-nism (2.13+/-0.38, P<0.01), PSP (2.36+/-0.36, P<0.01) and MSA (2.17+/-0.36, P<0.01). In patients with PD, early and delayed H/M ratios were significantly decreased in disease stages I, II and III (established using the Hoehn and Yahr criteria) as compared with control subjects, and there were no significant differences among the stages. Only PD showed a significantly higher washout rate (WR) than that in the control subjects (27%+/-8.0% vs. 11%+/-4.2%, P<0.01). Early and delayed uptake ratios of the lung, parotid gland, thyroid gland, liver and femoral muscles in each of the patient groups were not significantly different from those in control subjects. Only the early and delayed uptake ratios of the lower leg muscles in MSA were significantly lower than those in the control group (P<0.05). IN CONCLUSION: In patients with PD without autonomic failure, only cardiac MIBG uptake was severely reduced in the earliest phase of the disease (stage I). Parkinsonian syndromes other than PD did not demonstrate significant reduction in MIBG uptake in any organs except for the lower legs in MSA. In patients with PD without autonomic failure, reduction in MIBG uptake occurs selectively in the heart; this is considered to be a specific finding for PD and useful for the differential diagnosis of the parkinsonian syndromes.

[Autosomal dominant adult-onset spinal muscular atrophy with vocal cord paralysis: a case report].

This report concerns a 41-year-old female case of spinal muscular atrophy (SMA) associated with vocal cord paralysis. Her parents were not consanguineous. Her maternal grandmother and younger brother were suspected of having SMA. At age 37, she first experienced gait disturbance and began to have slowly progressive dysarthria and weakness of the extremities. Neurological examination revealed that she had inspiratory stridor, dysarthria and proximal muscular weakness of the extremities. Achilles tendon reflexes were absent, while there were no pathological reflexes or sensory disturbances. She showed a waddling gait and Gowers' sign. The laboratory data indicated mild elevation of serum CK. The nerve conduction study was normal, while the electromyographic study and muscle biopsy revealed neurogenic changes. We diagnosed the case as adult onset SMA of the autosomal dominant type. Laryngoscopy revealed that the patient had vocal cord paralysis, which was predominant in abductor muscles and of the posterior paralysis type according to the categories established by Isozaki. Genetic analysis showed no mutations in the genes of the neuronal apoptosis inhibitory protein and of the survival motor neuron.

[A patient with amnesic syndrome with defective route finding due to left posterior cerebral artery territory infarction].

We report a right-handed 67-year-old woman with an infarction in the left posterior cerebral artery territory presenting amnesic syndrome, right homonymous hemianopsia, pure alexia, color anomia, and defective route finding. The patient often walked in wrong directions out of her hospital room as well as in her home. She was able to recognize her own house and nearby streets by looking at them. Prosopagnosia and constructional impairment was not observed. Wechsler memory scale revised (WMS-R) revealed that she had marked disturbance in both visual and verbal recent memory. Brain MRI revealed an infarction involving the left medial inferior temporal and left medial occipital lobe, the left splenium of corpus callosum, and the left retrosplenial region. SPECT indicated a defect in the left medial occipital lobe and hypoperfusion in the left medial temporal lobe. Cerebral angiography demonstrated stenosis of the left medial occipital artery and occlusion of the left dorsal corpus callosal branches and the left calcarine artery. We conclude that left hippocampus, left parahippocampal gyrus and the left retrosplenial region may cause memory disturbance in our case. The lesion in the left retrosplenial region may have contributed to the occurrence of defective route finding. The relation between defective route finding and the retrosplenial amnesia is discussed.

Adenovirus-mediated transduction with human glial cell line-derived neurotrophic factor gene prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopamine depletion in striatum of mouse brain.

As a novel trial of neuroprotective therapy of neurodegenerative diseases, we have constructed a recombinant adenovirus vector (rAdv) bearing a neurotrophic factor gene to deliver the factor to rescue neurons in vivo. In the present study, human glial cell line-derived neurotrophic factor (hGDNF) was chosen to examine the applicability of our strategy to a mouse model of Parkinson's disease. During the construction of the rAdv, we found that the strong constitutive hGDNF expression unit somehow inhibited the appearance of the rAdv. Therefore we adopted a self-contained tetracycline-regulated expression system to acquire an rAdv expressing hGDNF. By analyzing the condition medium of SH-SY5Y cells infected with our constructed virus vector, we confirmed that biologically active GDNF was successfully expressed in vitro. For an animal study, we delivered this virus vector directly to the C57 black mouse brain and then exposed the animal to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to injure the nigrostriatal dopaminergic neurons. One week after the MPTP exposure, the neuroprotective effect of the virus vector was estimated by measurement of the dopamine content in the striatum of the mouse brain. The mice that had received our constructed virus had significantly higher dopamine levels in their striatum, demonstrating that our rAdv expressing hGDNF has therapeutic potential to protect the nigrostriatal dopaminergic neurons in vivo.

[Mixed transcortical aphasia due to multiple deep white matter infarction in the dominant cerebral hemisphere: a case report].

We report a case of mixed transcortical aphasia (MTA) due to multiple cerebral infarction in the dominant hemisphere in an 80-year-old right-handed woman without hemiplegia. Her spontaneous speech was markedly reduced and auditory comprehension, reading and writing were severely disturbed. Although the repetition of sentences (at most 3 words) was relatively preserved, her speech was echolalic. Brain MRI showed bilateral multiple deep white matter infarction and subcortical infarction of the left parietal lobe, including left angular gyrus, but no abnormal signal intensities were detected in either Wernicke's or Broca's area. SPECT indicated a significant decrease in mean cerebral blood flow in both hemispheres, but there was no focal hypoperfusion in either speech area. We thought that the focal hypoperfusion observed in the right cerebellum indicated crossed cerebellar diaschisis. Electroencephalogram showed a diffuse reduction in the incidence of alpha waves in the left cerebral hemisphere. From these findings, we suggest that widespread hypofunction in the dominant hemisphere was important for the occurrence of MTA.

[Body fat loss in patients with Parkinson's disease].

In order to investigate emaciation in patients with Parkinson's disease (PD), an anthropometric study was undertaken. In 59 out-patients (29 males, 30 females) with PD, the changes in body weight (delta BW) and in body mass index (delta BMI) were obtained and the ratio of body fat (% Fat) was measured with a bioelectrical impedance method. Twenty-two percent of the patients with PD had lost more than 10 Kg of BW (7% of males, 37% of females) and delta BW was -3.9 +/- 7.1 Kg, delta BMI -1.8 +/- 3.2 Kg/m2, and %Fat 25.9 +/- 5.6%. The reductions in both the BW and BMI of females with PD were significantly higher than for males (p < 0.003, p < 0.001, respectively). The disease duration had no correlation with delta BW or delta BMI, but a significant negative correlation with %Fat (all: p < 0.05; females: p < 0.03). However, no correlation was found between delta BW, delta BMI or %Fat on the one hand, and the disease severity or the total dosage of L-dopa with carbidopa on the other. We conclude that patients with PD, especially in females, experience gradual body fat loss according to disease duration.

Pure akinesia manifested neuroleptic malignant syndrome: a clinical variant of progressive supranuclear palsy.

An autopsy case of pure akinesia (PA) is reported. The patient manifested L-dopa-unresponsive akinesia without accompanying rigidity, tremor, eye movement disorder or dementia from the age of 58 years. Brain magnetic resonance T2-weighted imaging at the age of 63 showed high intensity areas in the subthalamic regions, but brain atrophy was not observed. She received amantadine-HCl and L-threo-3,4-dihydroxyphenylserine (L-DOPS) for 5 years. At the age of 66, she died of the severe illness accompanied by consciousness disturbances, hyperthermia, muscle rigidity, abnormal blood pressure and elevated serum enzymes which were derived from the muscle. We considered her condition to be neuroleptic malignant syndrome (NMS). Pathologically the brain revealed degeneration in the subthalamic nucleus, globus pallidus and substantia nigra. Neurofibrillary tangles were detected in the temporal cortex, hippocampus, amygdaloid body and spinal cord, as well as in the basal ganglia, thalamus and brain stem. These findings were consistent with that of progressive supranuclear palsy (PSP); the change in the ventral pons was insignificant, suggesting that PA may have minimum involvement in the ventral pons. The skeletal muscle showed scattered necrosis that was compatible with NMS. As far as we know, this is the first report of NMS accompanied with PA.

[Dystonic movement of the left upper limb in a case of the right pontine hemorrhage].

We report a 69-year-old woman who presented with dystonic movement in the left upper limb. She also had left hemiparesis and sensory disturbance in the right face and the left half of the body, pseudoathetosis in the left hand, and hotness, swelling, and lead-pipe rigidity in the left upper limb. The dystonic movement was presented mainly in the proximal part of the left upper limb, and was induced by voluntary movements; for example, when she was ordered to shake hands, the left shoulder always abducted with the flexion of the left elbow. Brain MRI showed a fresh hemorrhage in the dorsal part of the right middle pons including the base and the tegmentum, old infarctions in the right postero-lateral thalamus, putamen, and right parietal lobe. The dystonic movement persisted for 2 weeks, and hotness and swelling in the left upper limb lasted for 2 months, while the rigidity and pseudoathetosis persisted for 7 months or more despite medication.

Quantitative study of intermediolateral column cell counts in Machado-Joseph disease.

The number of intermediolateral column (ILC) neurons in 6 alternating segments from the 2nd to 12th thoracic segment of the spinal cord were studied in 4 cases with Machado-Joseph disease (MJD), 3 cases with olivopontocerebellar atrophy (OPCA), a case with Shy-Drager syndrome (SDS), and 5 normal controls. We counted the number of ILC neurons with clearly defined nucleoli in 12 sections of each segment, each section 20 microns thick and taken at 100 microns intervals and then divided the 6 alternating segments into 3 groups, upper (Th2, 4), middle (Th6, 8) and lower (Th10, 12). In each of the three groups of normal control cases, the number of ILC neurons had decreased with aging. In all MJD cases, the number of ILC neurons had moderately decreased in comparison with age-matched controls. One of the MJD cases showed a marked decrease in the number of ILC neurons, as did the SDS case. The ILCs of the entire thoracic spinal cord in the MJD cases were moderately involved.

A family with adult type ceroid lipofuscinosis (Kufs' disease) and heart muscle disease: report of two autopsy cases.

Two cases in a family with Kufs' disease had lethal arrhythmias and heart muscle disease. Autopsy findings showed an abundant accumulation of lipofuscin-like lipopigments in most neurons in the central nervous system (CNS). The heart showed a slight increase in the accumulation of the lipofuscin-like lipopigments in the myocardial fibers, slight to severe fibrosis and infiltration of fat cells in the myocardium. The lipopigments both in the heart and in neurons of the CNS had curvilinear profiles on electron microscope and reacted immunohistochemically to polyclonal antibodies against subunit c of mitochondrial adenosine triphosphate (ATP) synthase. The degenerative process in this heart muscle disease might be attributable to the same metabolic abnormality as seen in the neuronal degeneration associated with Kufs' disease.

Hereditary motor and sensory neuropathy associated with cerebellar atrophy (HMSNCA): a new disease.

Seven patients with hereditary motor and sensory neuropathy associated with cerebellar atrophy (HMSNCA) are presented. This is the first comprehensive evaluation of what is a unique disorder, half way between the cerebellar atrophies and the hereditary motor and sensory neuropathies. In addition to cerebellar ataxia and peripheral neuropathy, the most frequent features in HMSNCA were nystagmus, dysarthria, mental impairment and tremor. Pyramidal signs or autonomic nerve dysfunction was never revealed. Scoliosis or kyphoscoliosis was not noted. Progression of the disorder was very slow, most of the patients being ambulatory more than 10 years after the onset. Most of the patients had hypoalbuminemia. Half-life periods of serum albumin were normal and decreased synthesis of albumin in the liver was suspected. An autosomal recessive inheritance was strongly suggested, because of healthy consanguineous parents and affected siblings in these families. The segregation ratio was 0.32 +/- 0.10 and was close to the expected ratio of 0.25 in an autosomal recessive inheritance.

[A case of "apraxia of eyelid opening" secondary to right hemisphere infarction--assessment of various symptoms of the eye and eyelid].

A 68-year-old right-handed woman showed "apraxia of eyelid opening" during an acute phase of hemorrhagic infarction in the right middle cerebral artery distribution. She showed paradoxical contraction of the bilateral orbicularis oculi muscles both against our order to open her eyes and even against her hand-movement to help her eyes open, although she could voluntarily open her eyes. She was diagnosed as "apraxia of eyelid opening". Her eyes kept closed in most of time. Spontaneous blepharospasm and a right conjugate gaze preference were also seen. These symptoms disappeared 2 weeks after the hemorrhagic infarction. Because most of cases in previous reports as well as this patient showed "apraxia of eyelid opening" after a right cerebral involvement, we propose that this symptom may attribute to right cerebral dysfunction.

[Noradrenaline synthesis by locus coeruleus neurons transplanted in rat frontal cortex--influence of denervation of intrinsic noradrenergic projection].

Locus coeruleus (LC) noradrenergic neurons obtained from rat embryo (embryonic day 17) was prepared as cell suspension, and this neuronal cell suspension was transplanted in the frontal cortex of adult rats. The recipient rats were divided into 2 groups to examine the influence of the elimination of the intrinsic noradrenergic projection to the cortex on the transplanted neurons: the first group of animals received electric LC lesion 1 week prior to the transplantation (pre-lesioned group), and the second group received LC lesion 5 weeks after the transplantation (post-lesioned group). The animals were sacrificed 8 weeks after the transplantation, and the noradrenaline (NA) content in the frontal cortex was measured. The NA content in the frontal cortex was also measured 3 or 8 weeks after the LC lesion in the rats received no transplantation (without-T group). The NA content in the frontal cortex was 249 +/- 69 ng/g tissue weight (mean +/- SD, n = 7) in the pre-lesioned group and 252 +/- 69 (n = 11) in the post-lesioned group, while the NA content in the without-T group remained as low as 61 +/- 44 (n = 5) 3 weeks or 51 +/- 14 (n = 9) 8 weeks after the LC lesion. The differences of the NA content between the without-T group and the other two groups were statistically significant respectively. These results suggested that, both in the pre- and post-lesioned groups, the transplanted neurons survived in the recipient animal and synthesized substantial amount of specific neurotransmitter or NA.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of Wernicke-Korsakoff syndrome caused by gastrojejunostomy--specific findings of MRI and SPECT].

A 63-year-old woman with Wernicke-Korsakoff syndrome, despite the absence of alcoholism and malnutrition, is reported. She had undergone gastrojejunostomy for ileus 30 years ago, and this operation was thought to be an important risk factor for her vitamin B1 deficiency. Brain MRI showed symmetrical high intensity areas on T2-weighted images in the periaqueductal region and bilateral dorsomedial nuclei of the thalamus. On single photon emission computed tomography (SPECT) using 99mTc-hexamethylpropyleneamine oxime, bilateral frontal perfusion was reduced, which was attributed to thalamo-cortical diaschisis due to injury to the dorsomedial nuclei of the thalamus. Presumably this phenomenon explains the Korsakoff psychosis. A history of gastrojejunostomy, even if normal intake is possible, is a risk factor for vitamin B1 deficiency, and should be considered in the differential diagnosis of Wernicke-Korsakoff syndrome.

[Slowly progressive dysarthria and impaired language function--a case report].

A 68-year-old right-handed woman was admitted to Tokyo Metropolitan Geriatric Hospital because of slowly progressive dysarthria and writing disability over 2-year period. On admission, severe dysarthria was observed, but no dysphagia. The dysarthria mostly resembled a type of pseudobulbar palsy, although it was associated with effortful speech production. An oro-facial apraxia was also found. She could name objects, and could understand spoken words correctly. Examination using the Western Aphasia Battery showed diminution of word fluency, impaired repetition and perseveration and writing errors. On the Wechsler Adult Intelligence Scale-R verbal IQ was 100 and performance IQ was 87. These scores did not suggest any significant degree of general intellectual deterioration. Wisconsin card sorting test disclosed mild frontal dysfunction. Magnetic resonance imaging showed cortical atrophy in the bilateral frontal and temporal lobes. Measurements of regional cerebral metabolic rate by 18F-FDG-PET demonstrated decreased uptake in the latero-dorso-inferior area of the bilateral frontal lobes, especially on the left side. The present case showed slowly progressive dysarthria and progressive aphasia without generalized dementia, and without typical aphasia. These symptoms are speculated to be related to the atrophy in the bilateral frontal and temporal lobes shown by MRI and the decreased metabolic rate in the left dominant bilateral frontal lobes on PET study. The pathologic process responsible for these lesions remains obscure.

[Multiple mononeuropathy during recombinant interferon-alpha 2a therapy for chronic hepatitis C].

Reported is a case of multiple mononeuropathy which appeared during the administration of recombinant interferon-alpha 2a (rIFN-alpha 2a) for treatment of chronic hepatitis C. A 38-year-old man received an intramuscular injection of rIFN-alpha 2a, 6 x 10(6) IU, every one or two days for a nine week period. Seven weeks after the initiation of rIFN-alpha 2a therapy he developed numbness of the tongue and extremities and weakness of the upper extremities. Neurological examination revealed an asymmetrical disturbance of touch and pain sensation in the tongue, trunk, left shoulder and extremities accompanied by painful dysesthesia. Moderate weakness and muscular atrophy were noted in the right hand and left shoulder. Electrophysiological studies showed the amplitude of the compound muscle action potentials and sensory nerve action potentials were significantly decreased, when the right median and ulnar nerves were stimulated. Additionally, the conduction velocities were normal and needle electromyography showed fibrillation potentials suggesting an axonal form of multiple mononeuropathy. Biopsies of the muscle and nerve failed to show pathological changes, however. The clinical and electrophysiological abnormalities reduced gradually with methyl-prednisolone pulse therapy and administration of prednisolone and mizoribine. Therefore, in this case, administration of rIFN-alpha 2a may have induced multiple mononeuropathy of the axonal form.