An adult case of Chédiak-Higashi syndrome with parkinsonism and marked atrophy of the central nervous system

Chédiak-Higashi syndrome (CHS) is often a fatal disease of childhood characterized by oculocutaneous forms of albinism with congenital gigantism of peroxidase granules, granulation anomaly of leukocytes, hereditary gigantism of cytoplasmic organelles and a marked susceptibility to infections. A few patients have survived to age 20 years. A 39-year-old woman developed tremor and gait disturbance at age 22 years. At age 25 years, she was admitted to the Hospital for evaluation. Mental impairment, horizontal nystagmus, bradyphrenia, cogwheel rigidity, tremor at tongue, mandible and hands, bradykinesia, and unsteady gait were found and a juvenile parkinsonism was diagnosed. However, there was no favorable response by levodopa therapy. She became unable to walk at age 33 years. On admission, Oct. 27, 1988, at age 39 years, she was bedridden with a posture of decorticate rigidity. She was found to have partial depigmentation of the retina and choroid, pale and atrophic optic disc and subluxation of the mandible, Onuaguluchi's finger deformities and pes cavus. Neurological examination disclosed that she was alert but had marked difficulty in speaking. The communication was only possible by giving a sign of grasping of the left hand. The patient also showed oculogyric crisis, dystonic rigidity of the neck, diffuse muscular atrophy, complete paraplegia and decreased deep tendon reflexes with Babinski sign. On laboratory studies, at age 39, the white cells count was decreased (2,510/mm3), the hemoglobin level was 10.3 g/dl, the serum iron was 12 micrograms/dl, IgG 2,828 mg/dl, IgA 1,002 mg/dl, and the activity of natural killer cell was profoundly decreased (2%, normal; 18-40). Hematological examination revealed peroxidase positive giant granules in leukocytes. Chest X-ray film disclosed marked abnormal colon gas which located right subdiaphragma (Chilaiditi syndrome). Cerebrospinal fluid contained 12 cells/mm3, 99% lymphocytes; protein, 58.8 mg/dl; IgG, 6.8 mg/dl; HVA, 4.5 ng/ml (normal 41.8-44.6); 5-HIAA, 1.3 ng/ml (11.3-29.2); MHPG, 5.8 ng/ml (13.2-22.2).(ABSTRACT TRUNCATED AT 250 WORDS)     

Local cerebral glucose utilization in controlled graded levels of hyperglycemia in the conscious rat

Local cerebral glucose utilization assayed by the [14C]deoxyglucose ([14C]DG) method and calculated by means of its operational equation with values for the rate constants and lumped constant determined in rats under physiological conditions remains relatively stable with variations in arterial plasma glucose concentration within the normoglycemic range. Large changes in arterial plasma glucose level may, however, significantly alter the values of these constants and lead to artifactual results. Values for the lumped constant have been measured and reported for a wide range of arterial plasma glucose concentrations ranging from hypoglycemia to hyperglycemia in the rat (Schuier et al., 1981; Suda et al., 1981; Pettigrew et al., 1983). In the present study we have redetermined the rate constants in rats with arterial plasma glucose levels clamped at approximately 350, 450, and 550 mg/dl (i.e., 19, 25, and 31 mM) by a glucose clamp technique. The rate constants for the transport of DG from plasma to brain, K1*, and its phosphorylation in tissue, k3*, were found to decline with increasing plasma glucose levels, while the rate constant for its transport back from brain to plasma, k*2, remained relatively unchanged from its value in normoglycemia. These rate constants were used together with the previously determined values for the lumped constants to calculate local rates of cerebral glucose utilization in three groups of rats in which arterial plasma glucose levels were clamped at approximately 350, 450, and 550 mg/dl (i.e., 19, 25, and 31 mM). Average glucose utilization in the brain as a whole was unchanged in hyperglycemia from the values calculated in normoglycemic rats with the standard normal set of constants. Changes in the rate of glucose utilization were found, however, in the hypothalamus, globus pallidus, and amygdala during hyperglycemia.     

Effects of hyperglycemia or hypoglycemia on brain cell membrane function and energy metabolism during the immediate reoxygenation-reperfusion period after acute transient global hypoxia-ischemia in the newborn piglet

This study was done to determine the effects of hyperglycemia or hypoglycemia on brain cell membrane function and energy metabolism during the immediate reoxygenation-reperfusion period after hypoxia-ischemia (HI). Forty-five newborn piglets were divided randomly into four experimental groups: normoxia control (NC, n=9); HI/reoxygenation-reperfusion (RR) control (HC, n=11); HI/RR hyperglycemia (HE, n=12); and HI/RR hypoglycemia (HO, n=13) group. Animals were subjected to transient HI for 30 min followed by 2 h of RR. Cerebral HI was induced by temporary but complete occlusion of bilateral common carotid arteries with surgical clips and simultaneous breathing with 8% oxygen. Glucose was unregulated in HC group, and controlled by modified glucose clamp technique immediately after HI in HE (350 mg/dl) and HO (50 mg/dl) groups. During HI, heart rate, base deficit, glucose and lactate level in the blood and cerebrospinal fluid increased, and arterial pH, oxygen saturation and blood pressure decreased significantly in HC, HE and HO groups. During RR, these abnormalities returned to normal values, but lactic acidosis persisted especially in HO group. Cerebral Na(+),K(+)-ATPase activity decreased, and lipid peroxidation products increased significantly in HC group than in NC group, and these abnormalities were significantly aggravated in HE, but not in HO, group. Brain ATP and phosphocreatine levels in HE group were significantly reduced compared to the corresponding values in NC, HC and HO groups. In summary, hyperglycemia, but not hypoglycemia immediately after HI interfered with the recovery of brain cell membrane function and energy metabolism. These findings suggest that post-hypoxic-ischemic hyperglycemia is not beneficial and might even be harmful in neonatal hypoxic-ischemic encephalopathy.     

Cerebral mitochondrial respiration in diabetic and chronically hypoglycemic rats

The respiratory function of cerebral mitochondria harvested from genetically diabetic (BB/W) and streptozotocin-diabetic rats deprived of insulin for 3-4 weeks was found to be unchanged from control values. Furthermore, insulin-deprived BB/W rats subjected to 30 min of insulin-induced hypoglycemic coma demonstrated a normal mitochondrial respiration following a 60 min period of glucose restitution, a finding consistent with earlier results in non-diabetic rats. However, in rats exposed to 1 week of moderate hypoglycemia (plasma glucose = 3.0 mumol.ml-1), both state 3 respiration and the respiratory control ratio (RCR) were reduced from control. In fact, when the chronic hypoglycemia was imposed following a 3-4 week period of diabetic hyperglycemia, the state 3 rate and RCR were found to be reduced to a greater degree than in chronically hypoglycemic, non-diabetic, previously normoglycemic rats. Finally, when 1 week of moderate hypoglycemia preceded a 30 min period of insulin-induced hypoglycemic coma, a disturbed pattern of mitochondrial respiration (i.e. increased state 4, decreased RCR) was found at 60 min of recovery following coma. These results indicate that chronic increases in glucose (and insulin deprivation) have no effect on cerebral mitochondrial respiratory function, whereas prolonged, albeit moderate, reductions in cerebral glucose supply result in perturbations in mitochondrial respiration. These results demonstrate the importance of an adequate glucose supply for normal mitochondrial activity.     

Simple versus complex performance impairments at three blood glucose levels

By using a visual reaction time paradigm, we sought to determine if disruption of relatively simple responding (finger tapping or letter recognition) or more complex responding (choice reaction time) would occur in response to blood glucose deviations. Glucose levels were maintained in 24 male diabetics to within 4% of the following targeted concentrations: 55 mg/dl (hypoglycemia), 110 mg/dl (euglycemia/control), and 300 mg/dl (hyperglycemia). The results indicate that simple motor and perceptual skills were not affected by blood glucose alterations, while more complex cognitive processing required significantly longer response latencies during hypoglycemia. Performance impairments occurred independently of disease duration and control, and without documented neuropathy, underscoring the sensitivity of some cognitive skills to acute glucose fluctuations.     

Hyperglycemic brain injury in the rat

Children with diabetes onset before 5 years of age have reduced neurocognitive function. This problem has been attributed to hypoglycemia, a complication of insulin therapy. The eye, kidney, and nerve complications of diabetes (hyperglycemia) have been reduced by intensified insulin therapy which is associated with a 3-fold increase in severe hypoglycemia and therefore is not recommended for children less than 13 years of age. Since hyperglycemia is much more common than intermittent hypoglycemia during early childhood diabetes, it is important to determine if hyperglycemia affects brain growth and development. Rats were exposed to 4 weeks of either continuous hyperglycemia (diabetes) or intermittent (3 h, 3 times/week) hypoglycemia from 4 to 8 weeks of age. The brains of these animals were compared to those of similarly aged normal control animals. The cell number was increased, and the cell size reduced in the cortex of diabetic animals as assessed by DNA/wet weight of brain and protein/DNA content. Reduced amounts of protein, fatty acids, and cholesterol/microgram DNA also indicate smaller cells with reduced myelin content in the cortex of the diabetic animals. Histologic evaluation of these brains confirmed the biochemical findings. These observations require further confirmation and evaluation but indicate that continuous hyperglycemia may be more damaging than intermittent hypoglycemia to the developing brain. This is an important consideration for the management of diabetes mellitus in young children.     

Focal seizures in nonketotic hyperglycemia]

The cases of three patients with focal seizure associated to non-cetotic hyperglycemia are reported. Two patients presented motor epilepsy partialis continua (EPC). One case showed EPC as the first clinical manifestation of diabetes mellitus. Neurological exam was normal in all patients. CT and CSF were normal in the cases they were evaluated. Scalp EEG registered during a focal seizure revealed a bilateral temporal spiky activity. Glycemia levels were 455, 660 and 439 mg/dl. Two patients presented hyponatremia simultaneously. No patients had benefit with phenytoin or diazepam, and one patient got worse after them. Seizure control occurred after insulin and electrolytic treatment. It is important to diagnose this type of condition to avoid changes of non-cetotic hyperglycemia syndrome in a hyperosmolarity and coma state, disturbance which brings a higher mortality.     

Effects of hyperglycemia or hypoglycemia on brain cell membrane function and energy metabolism during the immediate reoxygenation–reperfusion period after acute transient global hypoxia–ischemia in the newborn piglet

This study was done to determine the effects of hyperglycemia or hypoglycemia on brain cell membrane function and energy metabolism during the immediate reoxygenation–reperfusion period after hypoxia–ischemia (HI). Forty-five newborn piglets were divided randomly into four experimental groups: normoxia control (NC, n=9); HI/reoxygenation–reperfusion (RR) control (HC, n=11); HI/RR hyperglycemia (HE, n=12); and HI/RR hypoglycemia (HO, n=13) group. Animals were subjected to transient HI for 30 min followed by 2 h of RR. Cerebral HI was induced by temporary but complete occlusion of bilateral common carotid arteries with surgical clips and simultaneous breathing with 8% oxygen. Glucose was unregulated in HC group, and controlled by modified glucose clamp technique immediately after HI in HE (350 mg/dl) and HO (50 mg/dl) groups. During HI, heart rate, base deficit, glucose and lactate level in the blood and cerebrospinal fluid increased, and arterial pH, oxygen saturation and blood pressure decreased significantly in HC, HE and HO groups. During RR, these abnormalities returned to normal values, but lactic acidosis persisted especially in HO group. Cerebral Na⁺,K⁺-ATPase activity decreased, and lipid peroxidation products increased significantly in HC group than in NC group, and these abnormalities were significantly aggravated in HE, but not in HO, group. Brain ATP and phosphocreatine levels in HE group were significantly reduced compared to the corresponding values in NC, HC and HO groups. In summary, hyperglycemia, but not hypoglycemia immediately after HI interfered with the recovery of brain cell membrane function and energy metabolism. These findings suggest that post-hypoxic–ischemic hyperglycemia is not beneficial and might even be harmful in neonatal hypoxic–ischemic encephalopathy.     

An autopsy case of spinal subdural abscess in the aged--comparative study with neuroradiological findings]

An 82-year-old woman without previous medical problem noticed vague back pain on December 31, 1989, and was admitted to a hospital because she developed a fever, a rapidly progressive weakness followed by anesthesia of the lower extremities and sphincter disturbance. On myelography and myelo-CT, the spinal cord appeared to be displaced by an extramedullary mass which partially blocked the subdural space at the level of T-9 to L-1. When transferred to our hospital on January 8, 1990, she was febrile and complaining of headache with meningeal signs. Percussion tenderness was present at T-8 to L-1 spinal spinous process. Neurological examination revealed that the patient had mild consciousness clouding, total paraplegia in the legs, sensory disturbance of a partial degree at L-1 to L-3 and totally below L-3, brisk but equal tendon reflexes in the upper extremities, areflexia in the legs with positive bilateral Babinski signs and sphincter disturbance. Otherwise she was neurologically unremarkable. Acute inflammatory reactions were prominent among the laboratory findings on admission. A lumbar tap yielded purulent fluid with more than 170,000 cells/mm3, 5,000 mg/dl of protein, 44 mg/dl of glucose and culture of the fluid isolated Escherichia coli. T1-weighted sagittal MRI disclosed an ill defined mass which showed the same or locally higher with gadopentetate dimeglumine (Gd-DTPA) signal intensity as soft tissue, compressing the spinal cord anteriorly from T-7 to L-3. The lesion was noticed to have a more extensive rostral-caudal extent than was inferred from myelography and myelo-CT.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lateral pontine and extrapontine myelinolysis associated with hypernatremia and hyperglycemia

Efforts to understand and prevent pontine and extrapontine myelinolysis have focused on the correction of hyponatremia, but controversy persists. We report a woman who presented in hyperosmolar diabetic coma with hypernatremia (169 mEq/l) and hyperglycemia (954 mg/dl). Plasma sodium rapidly increased to 188 mEq/l before gradually returning to normal. She remained obtunded and died 21 days later. Autopsy showed widespread, symmetrical demyelination involving the subcortical white matter, corpus callosum, anterior commissure, extreme, external, and internal capsules, fornix, thalamus, cerebellum, and lateral pons. The central pons and lateral geniculate nuclei were uninvolved. This case illustrates that lateral pontine and extrapontine myelinolysis can be associated with hypernatremia and hyperosmolality. In both hypo- and hypernatremic states, the significant event may be an increase in serum sodium or serum osmolality of sufficient rapidity and magnitude.     

Protective effect of dexamethasone on osmotic-induced demyelination in rats

Central pontine myelinolysis (CPM) is a serious demyelination disease commonly associated with the rapid correction of hyponatremia. Although its pathogenesis remains unclear, the disruption of the blood-brain barrier (BBB) as a consequence of a rapid increase in serum sodium concentration is considered to play a critical role. Since glucocorticoids are known to influence BBB permeability and prevent its disruption as a result of hypertension or hyperosmolarity, we investigated whether dexamethasone (DEX) could protect against osmotic demyelination in an animal model of CPM. Hyponatremia was induced in rats by liquid diet feeding and dDAVP infusion. Seven days later, the animals' hyponatremia was rapidly corrected by injecting a bolus of hypertonic saline intraperitoneally. Rats subjected to this treatment displayed serious neurological impairment and 77% died within 5 days of rapid correction of their hyponatremia; demyelinative lesions were observed in various brain regions in these animals. On the other hand, rats that were treated with DEX (2 mg/kg, 0 and 6 h after hypertonic saline injection) exhibited minimal neurological impairment and all were alive after 5 days. Demyelinative lesions were rarely seen in the brains of DEX-treated rats. A marked extravasation of endogenous IgG was observed in the demyelinative lesions in the brains of rats that did not receive DEX, indicating disruption of the BBB, but was not observed in DEX-treated rats. Furthermore, Evans blue injection revealed a significant reduction in staining in the brains of DEX-treated rats (P < 0.05). These results indicate that early DEX treatment can prevent the BBB disruption that is caused by the rapid correction of hyponatremia and its associative demyelinative changes, and suggest that DEX might be effective in preventing CPM.     

A case of central pontine myelinolysis with neurological recovery after administration of glucocorticoid

A survival case of central pontine myelinolysis (CPM) is reported herein with a review of 22 MRI-analyzed CPM survivors in the literature. A 65-year-old male was struck on the forehead while in a traffic accident. He was almost fully conscious and neurologically free on admission. Laboratory data were normal except hyponatremia [122 mEq/l] and hypoproteinemia [5.8 g/dl]. 2 hours later he became drowsy and left hemiparesis. The CT scan showed right frontal cerebral hematoma leading to a remarkable midline shift. Immediately, aspiration of the hematoma was performed. On the next day, he returned to the initial neurological level. On the third day, however, he again became comatose followed by tetraparesis and ataxic respiration. While the CT scan at that time did not display any abnormality in the pons, the severe dysfunction of the brain stem occurred after the correction of hyponatremia strongly suggesting CPM. The serum Na levels were kept between 110 and 125 [mEq/l]. In addition, 375 mg of methylprednisolone had been daily administrated during and after a gradual correction of the hyponatremia, because glucocorticoid proved to be effective in the models of CPM. The neurological condition began to improve on the 14th day after admission. Eventually, he became conscious and independent in his daily activities, the time span being 8 months after the trauma. The trident MRI lesion in the basis pontis was 5 mm in diameter and much smaller than clinically expected. The 23 MRI-analyzed CPM survivors were reviewed in the literature including the present case. There were 7 males and 16 females, with a mean age of 48.5 years.(ABSTRACT TRUNCATED AT 250 WORDS)     

An adult case of probable Bassen-Kornzweig syndrome, presenting resting tremor]

We report a 53-year-old woman with probable Bassen-Kornzweig syndrome. Her parents were a consanguineous marriage. At two years of age, she developed night blindness. During her childhood she had severe diarrhea that disappeared in adulthood. At 26 years of age, she was diagnosed as having retinitis pigmentosa and her visual acuity became worse thereafter. She noted tremor in the right hand at 37 years of age, gait ataxia at 42, and developed tremor in the bilateral lower extremities at 48. On admission, bilateral visual disturbance, resting and postural tremor, moderately poor coordination, mild distal dominant sensory impairment, an absence of tendon reflex in all four extremities, moderate to severe gait ataxia, and positive Romberg sign were found. Muscle rigidity and akinesia were not observed. Intelligence and muscle power were normal and pathological reflexes were absent. Acanthocytes were found in blood. Serum chemistry showed remarkable decreases in total cholesterol (54 mg/dl, normal 180-220), triglyceride (0 mg/dl, normal 30-150), beta-lipoprotein (3 mg/dl, normal 190-500), apoA-1 protein (66 mg/dl, normal 105-184), apoA-2 protein (11 mg/dl, normal 26-46), apoB protein (0 mg/dl, normal 38-104), apoC-2 protein (1.1 mg/dl, normal 1.2-6.4), vitamin A (297 ng/ml, normal 431-1,041), and vitamin E (0.19 ng/dl, normal 0.75-1.41). While, a marked increase in PIVKA II (703 mAU/ml, normal<40) due to a decrease in vitamin K was found. She was thus diagnosed as having Bassen-Kornzweig syndrome or hypo-betalipoproteinemia. Although brain MRI was normal, single-photon emission CT (SPECT) showed mildly decreased perfusion in the left parietal cortex and right striatum. Motor nerve conduction velocities were normal, but sensory nerve action potentials were not evoked in all four extremities. Surface EMG recorded on the right radial extensor and flexor carpi muscles at rest showed a 4.5 Hz tremor. Vitamin replacement therapy with vitamin A (10,000 IU/day), E (200 mg/day), and K (10 mg/day) was initiated. Several days after treatment, amplitude of resting tremor ameliorated mildly. Clonazepam was administered (0.5 mg/day) for further treatment. After one-month of treatment, vitamin A (656 ng/ml) and E (0.39 mg/dl) levels were elevated and PIVKA II level (29 mAU/ml) decreased. Only a mild right hand tremor remained, but sensory impairment and gait ataxia were not changed. The cause of Bassen-Kornzweig syndrome is a deletion of the microsomal triglyceride transfer protein (MTP) gene. While, familial hypo-betalipoproteinemia, due to a mutation of apolipoprotein B gene, is known to show the same phenotype. Because of the patient's refusal of genetic examination, which disease she has cannot be conclusively determined. Intention tremor was reported in Bassen-Kornzweig syndrome. However, her 4.5 Hz tremor was also present at rest, which resembled resting tremor in Parkinson's disease. Pathophysiology of Bassen-Kornzweig syndrome is known to be due to hypo-vitaminosis. Decreased [18F]-dopa uptake in striatum of patients with long-term hypo-vitamin E has been reported in PET study. Mild hypoperfusion was found in the striatum of the present cases: indicating that her tremor was associated with striatonigral damage. Thus, careful observation of extrapyramidal signs is necessary in abeta- or hypo-betalipoproteinemia.     

Hypoglycemic hemiplegia: a report of three cases]

Hemiplegia is a rare complication accompanied with hypoglycemia. We reported three cases of hypoglycemic hemiplegia (HH). Case 1: A 74-year-old female had medication for diabetes mellitus (DM). She had right hemiplegia and aphasia. Case 2: A 72-year-old male had DM, and was admitted to our hospital having loss of consciousness and right hemiplegia. Case 3: An 82-year-old female suffered from consciousness disturbance with tetraplegia, and had left hemiparesis later. She had no DM, but suffered from iatrogenic hypoglycemia. The brain CT of these three cases showed atrophy, and MRI demonstrated multiple infarction. The angiography of case 1 showed the stenosis of bilateral internal carotid artery and the origin of the left vertebral artery. The angiography of case 2 showed severe stenosis of the left internal carotid artery. The cases above had hypoglycemia at admission. The value of the case 1 was 48 mg/dl, case 2 was 35 mg/dl and case 3 was 38 mg/dl. But these symptoms of the three cases disappeared rapidly after glucose infusion. The literature regarding HH was reviewed, and the pathogenesis was discussed. We emphasize the importance of checking blood sugar levels for the emerging patients with hemiplegia, because it is difficult to discriminate by clinical history or neurological findings.     

A 73-year-old woman with familial Parkinson's disease]

We report a 73-year-old Japanese woman with familial Parkinson's disease. The patient was well until her 67 years of the age, when she noted rest tremor in her right hand. Soon after her gait became short stepped. She visited our clinic on October 6, 1992 when she was 68 years old. She was alert and well oriented without dementia. She showed masked face, small voice, small stepped gait, retropulsion, resting tremor in her right hand, rigidity in the neck, and bradykinesia. She was treated with 400 mg/day of levodopa-carbidopa, which improved her symptoms, however, she developed wearing off phenomenon 3 years after the initiation of levodopa treatment. On August 26, 1998, she developed abdominal pain, diarrhea, and vomiting. She was admitted to another hospital, where abdominal plain x-ray revealed an evidence of intestinal obstruction (ileus). She was treated with nasogastric suction and intravenous fluid. Her condition did not improve and she was transferred to our hospital on August 29, 1998. Her family history revealed no consanguineous marriage. She had two elder brothers and three elder sisters. One of her brothers had been diagnosed as Parkinson's disease. Her husband also suffered from Parkinson's disease, however, her parents apparently did not have Parkinson's disease. On admission, she appeared to be drowsy. Her blood pressure was 102/70 mmHg, body temperature 36.2 degrees C. The lungs were clear and no cardiac murmur was present. Abdomen was flat and bowel sound was audible. No abnormal mass was palpable. Neurologic examination revealed mild consciousness disturbance, masked face, and small voice. No motor paralysis was noted. Muscle tone was hypotonic. No abnormal involuntary movement was noted. Abnormal laboratory findings on admission were as follows; WBC 11,300/microliter, amylase 1,373 IU/l, CK 446 IU/l, BUN 50 mg/dl, creatinine 1.17 mg/dl, CRP 22.7 mg/ dl, Na 134 mEq/l, K 3.1 mEq/l, and Cl 81 mEq/l. A chest x-ray film revealed pneumonic shadows in both lower lung fields. She was treated by nasointestinal suction, intravenous fluids, and chemotherapy for her infection. Her BP started to drop on September 2 and she developed cardiac arrest on the same day. She was discussed in a neurological CPC. The chief discussant arrived at the conclusion that the patient had a form of autosomal dominant familial Parkinson's disease. As parents did not have Parkinson's disease, some of the participants raised the possibility of autosomal recessive inheritance. But the age of onset was too late for autosomal recessive inheritance. Majority thought that the mode of inheritance was autosomal dominant with low penetrance. alpha-Synuclein mutation causes an autosomal dominant familial Parkinson's disease, but this type is very rare in non-Greek populations and the penetrance is high. Chromosome 2-linked autosomal dominant familial Parkinson's disease shows low penetrance. There are many other autosomal dominant forms of familial Parkinson's disease linked to yet unknown chromosome loci. Majority thought that this patient also had a form of Lewy-body positive autosomal dominant familial Parkinson's disease of unknown chromosome locus. Post mortem examination revealed ischemic intestinal lesion with strangulation. This was thought to be the cause of her death. In the central nervous system, the brain appeared to be normal by inspection. In the coronal sections, the substantia nigra and the locus coeruleus showed marked depigmentation. Histologic examination revealed marked neuronal loss and Lewy body formation in the remaining neurons. Pathologic examination was consistent with Parkinson's disease. Mutational analysis for the parkin gene was negative.     

Hypoglycemic encephalopathy with extensive lesions in the cerebral white matter

Here we report an autopsy case of hypoglycemic encephalopathy with prolonged coma. Laboratory data obtained when the patient lapsed into a coma showed that she had a low level of serum glucose (27 mg/dL). Although the level of glucose returned to within the normal range rapidly after glucose infusion, the patient remained in a coma for 22 months. It was presumed that the state of hypoglycemia persisted for about 4 h. There was no evidence of hypotension or hypoxia. Magnetic resonance imaging was performed 3 h after glucose administration; diffusion‐weighted images revealed hyperintensity in the cerebral white matter and in the boundary zone between the middle and posterior cerebral arteries. Post‐mortem examination revealed superficial laminar necrosis throughout the cerebral cortex. Neuronal necrosis was also found in the hippocampus and dentate gyrus, although the CA3 region appeared normal. In addition to these lesions, which are consistent with hypoglycemia‐induced brain damage, the cerebral white matter exhibited severe loss of myelin and axons with reactive astrocytosis and macrophage infiltration. Old infarcts were also present in the bilateral occipital lobes. Since the cerebral blood flow is reported to be decreased during severe hypoglycemia, the present findings suggest that white matter lesions and boundary‐zone infarctions may develop primarily in uncomplicated hypoglycemia.     

A case of alcoholic with vitamin B12 deficiency presenting central pontine and extrapontine myelinolysis on MRI]

A 55-year-old man with chronic alcoholism was first referred to us in 1992 because of spastic quadriparesis. T2-weighted images of MRI showed pontine and extracapsule lesions as central pontine and extrapontine myelinolysis (CPM/EPM). He had macrocytic anemia with normal serum level of vitamin B12 (B12). Gait disturbance was progressively worsened from the end of 2004 and dysuria appeared from June, 2005. Neurological examination on admission in November, 2005, showed mild impairment of recent memory, spastic paraparesis with hyperreflexia in all limbs, loss of deep sensations in lower limbs and urinary disturbance. The low serum level of B12 with marked macrocytic anemia was noted. On MRI. the pontine lesion extended to the midbrain but no abnormality was found in the spinal cord. We intramuscularly administered B12, resulting in marked improvement of both anemia and neurological symptoms. The brainstem lesion on MRI, however, was unchanged. We assume that B12 deficiency was involved in the formation of CPM/EPM and the neurological symptoms in our patient.     

MRI findings of brain-stem tuberculoma in a case of tuberculous meningitis]

A 54-year-old woman developed headache and slight fever. When she consulted a physician, she could not move either of her eyes to the right. Cranial CT scan revealed no significant findings. Lumbar puncture was performed and CSF examination showed the cell count of 10,304/mm3, glucose level of 10 mg/dl, and total protein value of 270 mg/dl. Her symptoms and laboratory findings suggested meningitis and she was admitted to our hospital. Neurological examination revealed bilateral dilated pupils with sluggish light reflex, right gaze palsy, and hypesthesia of the left side of her face. A diagnosis of tuberculous meningitis was established by a positive test for acid-fast bacillus in CSF, and anti-tuberculous therapy was started at once. One month after the onset of symptoms, her main complaints were double vision and cerebellar ataxia. Both CT and MRI revealed a right brain-stem lesion. Pre-contrast CT could not clearly visualize the lesion but with contrast medium a homogeneously-enhanced circular lesion was shown. MRI on T2WI demonstrated the right brain-stem lesion to have a central bright core with hypointense periphery, which in turn was surrounded by hyperintensity. The lesion appeared isointense with cerebral white matter and the "central bright core" area was demonstrated to be slightly hypointense on T1WI. On post-contrast T1WI (with Gd-DTPA), the lesion showed strong homogeneous enhancement. The CT and MRI findings indicated a brain-stem tuberculoma, which was regarded as the cause of the ocular movement paralysis and cerebellar ataxia. As the clinical symptoms gradually resolved with anti-tuberculous treatment, the MRI appearance of the lesion also improved.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prolonged hyperglycemia in the early subacute period after cerebral infarction: effects on short term prognosis

Although the adverse effect of admission hyperglycemia in cerebral infarction on prognosis is well known, studies generally have not questioned the effect of hyperglycemia in the early subacute period on prognosis after a stroke. Forty-six patients with acute ischemic stroke were seperated into 3 groups: Group 1) Known diabetes or admission blood glucose (ABG) > or = 140 mg/dl and HbA1c > or = 8,0%); Group 2) ABG > or = 140 mg/dl and HbA1c < 8,0%; and Group 3) ABG < 140 mg/dl and HbA1c < 8,0%. Blood glucose was followed-up 4 times a day for 10 days after the stroke and the mean of these measurements was calculated as the mean of glycemic regulation (MGR). Neurological evaluation was done at presentation and on day 10 and 30 with the National Institute of Health (NIH) scale. Oedema, lesion size and presence of hemorrhagic transformation were evaluated using CT. The MGR was significantly higher in group 1 compared to the other two groups (p < 0,001 and p < 0,01) and in group 2 compared to group 3 (p < 0,001). Patients with clinical worsening had a significantly higher MGR (p < 0,05). Patients with marked cerebral edema had a significantly higher MGR (p < 0,01) compared to patients with lesser edema. No correlation was found between MGR and lesion size or hemorrhagic transformation. Our results show that hyperglycemia in the early subacute period after cerebral infarction is associated with more pronounced cerebral edema and has an adverse effect on short term prognosis. We suggest that studies investigating the effect of insulin infusion on stroke prognosis should also consider infusions for a longer period than 24 hours.     

Successful treatment of levodopa-induced neuroleptic malignant syndrome (NMS) with disseminated intravascular coagulation (DIC) in a patient with Parkinson's disease

A 77-year-old woman with a 9 years history of Parkinson's disease was admitted to our hospital because of high fever, disturbance of consciousness, increased muscular rigidity and abnormal involuntary movements. She was continuously treated with levodopa + carbidopa (Menesit) 300 mg and amantadine 150 mg every day until admission. On admission, the pulse rate was 102 per minute, blood pressure 90/40 mmHg, body temperature 40.9 degrees C, and bloody stool was noticed. On laboratory examination, erythrocyte sedimentation rate was 6 mm/h, thrombocytes 8.1 X 10(4)/microliters, fibrinogen 91 mg/dl, FDP 40 mg/ml, suggesting DIC. According to her biochemical examination, serum GOT (167 u), GPT (119 u), CPK (847 IU/l), BUN (53.9 mg/dl) and myoglobin (10,370 ng/ml) were increased. These laboratory data indicated that she was suffering from neuroleptic malignant syndrome (NMS) with disseminated intravascular coagulation (DIC). On diagnosis of NMS associated with DIC, she was treated with dantrolene and FUT-175. Dantrolene was effective on the elevated COK level and FUT-175 was effective on the DIC, and symptoms of NMS and DIC were completely improved after a period of 14 days. Patients with Parkinson's disease have been suspected to have a low incidence of DIC, and this may be the first case report on successful treatment of levodopa-induced NMS with DIC in the patient with Parkinson's disease.