Multiparametric analysis of cerebral substrates and nitric oxide delivery in cerebrospinal fluid in patients with intracerebral haemorrhage: correlation with hemodynamics and outcome.

BACKGROUND: There is no information regarding the possible role of cerebral substrates in the pathogenesis of neuronal injury in intracerebral haemorrhages (ICHs). Purposes of this prospective study were to clarify whether changes in substrates are the consequence of the initial brain damage in ICH and to elucidate the relationship among the biochemical mechanisms and clinical course of patients with ICH. METHOD: During a period of two years, patients (GCS < or =8) who had ICH secondary to an aneurysm (SAH), stroke (sICH), or trauma (tICH) and underwent ventriculostomy with ICP monitoring and/or underwent cranial surgery were randomly enrolled in this study. Extracellular concentrations of glutamate, aspartate, glycine, GABA, lactate, lactate/pyruvate ratio, and glucose in the CSF were measured by use of high-performance liquid chromatography (HPLC). The nitric oxide (NO) concentration in the CSF was analyzed by chemiluminescence. FINDINGS: There were 75 patients (38 women and 37 men) with ICH included in this study. Twenty-one patients had SAH, 28 sICH, and 26 tICH. In tICH patients, there was a 30-fold increase in glutamate and a 10-fold in aspartate over reference values. The levels of glutamate, aspirate, GABA, lactate, glucose, and NO differed significantly among the three groups (p<0.001). There were no significant differences in glycine and L/P ratio among the groups. The initial GCS, the mean CPP and outcome six months after the insult were all significantly correlated with the concentration of substrates (p<0.01), both within groups and among the total sample. The CSF levels of glutamate lactate, NO and glucose correlated significantly with outcome (p<0.005). CONCLUSIONS: This study confirms the correlation between the level of EAAs and the outcome of ICHs, suggesting that neurochemical monitoring of these substances may have a role in caring for patients.

Crossed cerebellar diaschisis in herpes simplex encephalitis.

Diaschisis is extremely rare in patients with viral encephalitis. We report the phenomenon of crossed cerebellar diaschisis (CCD) in a 73-year-old man with acute herpes simplex type-1 (HSV-1) encephalitis. The diagnosis of HSV-1 encephalitis was confirmed by detecting HSV-1 deoxyribonucleic acid in the cerebrospinal fluid (CSF). Magnetic resonance images (MRI) showed enhancing lesions at bilateral temporal lobes, insular cortices, and right frontoparietal lobes. Increase signal intensity on T2-weighted images was seen in the mesecephalon. Technetium-99m ethyl cysteinate dimer (99mTc-ECD) single photon emission computed tomography (SPECT) of the brain showed a large area of hypoperfusion in the right frontotemporoparietal lobes. The side-to-side cerebellar count revealed 19% reduction of the radioisotope tracer uptake in the left cerebellum. The phenomenon of CCD was proposed to be due to both anterograde disconnection of the corticopontocerebellar tracts and retrograde deafferentation of dentatothalamocortical projections.

Cerebral and oculorhinal manifestations of a limited form of Wegener's granulomatosis with c-ANCA-associated vasculitis.

The authors report on cerebral and oculorhinal manifestations in a patient with a cytoplasmic pattern of antineutrophil cytoplasmic autoantibody (c-ANCA)-associated vasculitis. Recurrent Tolosa-Hunt syndrome, cavernous sinus syndrome, Raeder's paratrigeminal neuralgia, and seizures were the major clinical manifestations. Brain MRI showed localized enhancing lesions initially in the cavernous sinus and later in the convexity pachymeninges. The lesions disappeared following 9 months of oral prednisolone (15 mg/day) and cyclophosphamide (100 mg/day) therapy. The presence of c-ANCA, demonstration of vasculitis, and depositions of immunoglobulin G (IgG) and fibrinogen in the vessel walls of pachymeninges of the patient confirmed an immune-mediated cause of the vasculitis. Cranial pathology without renal and pulmonary involvement suggests a variant of Wegener's granulomatosis, which is called the "limited" form of Wegener's granulomatosis. MRI, Raeder's paratrigeminal neuralgia, localized pachymeningitis.

Phenotypic heterogeneity in a Chinese family with mitochondrial disease and A3243G mutation of mitochondrial DNA.

The A3243G mutation of mitochondrial DNA (mtDNA) has been shown to be responsible for or associated with mitochondrial myopathy, encephalopathy, lactic acidosis, strokelike episodes (MELAS) syndrome, diabetes mellitus (DM) and several other neuromuscular diseases. We used polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) to identify the A3243G mtDNA mutation and an electron microscope to examine mitochondrial derangement in the muscle biopsies of a 38-year-old man suspected to have MELAS syndrome with DM. We found great variability in the clinical presentation and in the proportion of mtDNA with the A3243G mutation in the matrilineal family members of the patient. The proband had atypical MELAS syndrome, recurrent vascular headache, and DM (MELASDM), and his mother manifested chronic progressive ptosis and DM (CPPDM). Brain magnetic resonance imaging of the proband showed high signal intensity in the left temporoparieto-occipital area on T2 weighted images (T2WI). The blood lactate level ranged from 2.32 to 4.70 mmol/l, and two-hour postprandial glucose ranged from 124 mg/dl to 148 mg/dl. The blood lactate and postprandial glucose of the proband's mother were 3.15 mmol/l and 192 mg/dl, respectively. Electron microscopic examination of a muscle biopsy of the patient showed abnormal mitochondria with decreased density of cristae and membrane degeneration. No ragged-red fibers were detected in muscle upon staining with modified Gomori trichrome. The hair follicles and blood cells of the patient and his mother showed the A3243G mutation in the tRNA(Leu)(UUR) gene. The proportions of the mutant DNA in the hair follicles and blood cells of the proband were 36.8% and 35.2%, respectively, and those of the patient's mother were 28.8% and 13.9%, respectively. We conclude that the A3243G mtDNA mutation may manifest with MELASDM or CPPDM in different matrilineal members of the same family as a result of differences in random segregation of the heteroplasmic A3243G mutant mtDNA in the affected tissues of patients.

Diaschisis in chronic viral encephalitis with Koshevnikov syndrome.

The authors report a 61-year-old man with chronic viral encephalitis and Koshevnikov syndrome occurring 42 months after initial symptom of right hemiparesis. Serial computed tomography of the brain showed changes in the attenuation of the left temporal lobe lesion over time. Magnetic resonance images of the brain showed enlargement of left temporoparietooccipital lobes with cortical gyral enhancement on T1-weighted images following intravenous administration of gadolinium-DTPA. 99mTc-HMPAO single-photon emission computerized tomography showed increased radioactivity and hyperperfusion in the left temporoparietal region with paradoxically decreased local tissue perfusion at the contralateral right hemisphere. Follow-up magnetic resonance images of the brain 4 years later showed atrophy of bilateral cerebral hemispheres. We postulate that a "transcallosal diaschisis" with subsequent degeneration is a possible mechanism. A brain biopsy from the left temporal lobe lesion showed pictures compatible with viral encephalitis probably herpes simplex encephalitis.

Neurotrophic factors increase tyrosine hydroxylase immunoreactive cell density of fetal mesencephalic cells.

OBJECTIVE: To hibernate fetal ventral mesencephalic tegmental (VMT) cells from Spraque-Dawley rats E-15 for 5 days at 4 degrees C in either hibernation media (HM) or in conditioned hibernation media (CHM) supplemented with trophic factors such as epidermal growth factor (EGF 200 ng/ml), basic fibroblast growth factor (bFGF 100 ng/ml), recombinant human brain derived neurotrophic factor (rhBDNF 20 micrograms/ml), recombinant human glial cell-derived neurotrophic factor (rhGDNF 20 micrograms/ml), fetal calf serum (FCS 9%), or human placental cord serum (HPCS 10%). METHODS: The percent of cell viability and the density of tyrosine hydroxylase immunoreactive (THir) cells in fetal striatal-VMT co-culture were determined. RESULTS: The viability of fetal striatal cells (0.8 +/- 0.104) was slightly higher than that of fetal VMT cells (0.7 +/- 0.072) at 0-time point (F17,1 = 4.677; P = 0.045). After 5 days of hibernation, the viability of fetal VMT cells reduced by 30% (F7,1 = 88.493; P < 0.001) in HM. However, THir-cell density reduced by more than 90% as compared to the freshly harvested VMT cells (F7,1 = 179.944; P < 0.001). CHM with HPCS, bFGF, EGF, BDNF, and GDNF showed higher THir-cell density than that of HM or CHM supplemented with FCS (P < 0.001). CONCLUSION: Supplementation of appropriate trophic factors for hibernated fetal VMT cells promotes cell viability and the subsequent expression of THir-cell density.

The effects of storage conditions and trophic supplementation on the survival of fetal mesencephalic cells.

It is estimated that only 5-10% of dopamine (DA) neurons implanted into the striatum of patients undergoing fetal-nigral transplantation as a treatment for Parkinson's Disease survive. Because it is often necessary to store fetal tissue prior to transplantation, we evaluated various storage parameters that could influence DA neuron viability in rostral mesencephalic tegmentum (RMT) cultures using tyrosine hydroxylase immunoreactive (THir) cell counts as an index of DA neuron survival. A high K+ hibernation media (HM) was used in all studies. We found that RMT cell viability and THir cell counts decreased as storage duration increased (up to 120 h). Storage at 37 degrees C in HM killed all cells, while storage at 10 degrees C yielded higher survival rates than 4 degrees C. In comparison to trypsinization, mechanical dissociation of tissue increased cell viability. Neutral pH and a storage density of at least 1 x 10(6) cells/mL were found to be optimal, while striatal coculture of RMT cells with striatal feeder layers increased THir viability up to 16-fold in comparison to monocultures. The nurturing effect of striatal coculture may be explained by the release of autotrophic factors, and we tested this hypothesis by supplementing the HM with human placental cord serum (HPCS, 8%), glial-derived neurotrophic factor (GDNF; 10 microg/mL), and brain-derived neurotrophic factor (BDNF; 10 microg/mL). GDNF and HPCS supplements increased RMT cell viability by 10-15%, while GDNF, BDNF, and HPCS increased viability of THir cells by approximately 40% at all time points studied. As Klenow enzyme labeling technique indicated that 33% of stored RMT cells were undergoing apoptosis, we found that GDNF, BDNF, and HPCS reduced apoptosis by 50%. DNA laddering and DAPI nuclear stain confirmed the presence of apoptosis in hibernated RMT cells, leading us to postulate that the high viability counts seen with trypan blue exclusion are misleading.

The syndrome of delayed posthemiplegic hemidystonia, hemiatrophy, and partial seizure: clinical, neuroimaging, and motor-evoked potential studies.

Magnetic motor-evoked potential (MEP) study of patients with the syndrome of delayed posthemiplegic hemidystonia, hemiatrophy, and partial or hemi-seizures ('4-hemi' syndrome) has not been described. Among 35 patients investigated for posthemiplegic movement disorders from February 1988 to January 1995, seven showed '4-hemi' syndrome. Clinical work-up, magnetic resonance images (MRI) and/or computed tomography (CT) were performed in all. Transcranial MEP studies were done in five patients. The remote causes of '4-hemi' syndrome were neonatal stroke, trauma, and encephalitis in infancy. The dystonia may occur as long as a decade after the initial insult. MRI or CT showed destructive lesion in the contralateral putamen (five patients), caudate (four), thalamus (five), and atrophy of the contralateral hemisphere (five). Other associations were porencephalic cyst. Wallerian degeneration, and asymmetric compensatory ventriculomegaly. MEP showed abnormalities in the affected upper limbs in four of five patients. The abnormalities were reduced amplitude of the compound muscle action potential following cortical stimulations with or without temporal dispersion, and with or without prolongation of its latency. The peripheral motor conductions following cervical stimulations were normal. MEP abnormalities may not be related to the hemiatrophy and the size of brain lesion per se. The hemidystonia is static after the second decade of life, and it is often difficult to treat.

MRI appearance of spinal lesions: metastatic tumors or infections?

Three patients with pathologically verified spinal osteomyelitis and another three with metastatic tumors of the spine were investigated. MRI of th spine of four patients showed several unusual findings. The preservation of intervertebral discs and endplates did not predict accurately the diagnosis of either infections or tumors. The "pepper and salt" appearing feature may also occur in a metastatic tumor. Plain radiographs, CT, and radioisotope bone scans were less sensitive than MRI to disclose the lesions. In cases of osteomyelitis, the systemic sources of infections were frequently not found, and the responsible microorganisms could not be identified even from the surgical specimens of two patients. However, mycobacterium tuberculosis was found in the surgical specimen of a patient with cervical spinal lesion whose MRI was indistinguishable from a metastatic tumor. Surgicopathological diagnosis was therefore crucial and mandatory in these instances.

Progressive late delayed postirradiation encephalopathy with Klüver-Bucy syndrome. Serial MRI and clinico-pathological studies.

The first pathologically documented case of progressive late delayed postirradiation encephalopathy in a 37-year-old man with Klüver-Bucy syndrome (KBS) is reported here. The pathological findings and clinical course of KBS with recurrent stroke-like episodes and partial epilepsy within a 7-year period following a 'safe dose' radiation therapy for pituitary tumor are presented. Serial magnetic resonance imaging shows, at different stages of the disease, a pontine infarct, enlarged temporal lobes with serpentine hyperintense signal at cortical gyri on T2-weighted and proton density MRI, and progressive brain calcification which appears hyperintense on T1-weighted images and hypointense on T2-weighted images.

Acute intermittent porphyria: clinical analysis of nine cases.

BACKGROUND: Acute intermittent porphyria (AIP) is an uncommon disorder, characterized by a variety of nonspecific symptoms and signs. Many patients have undergone prolonged medical care for the condition without accurate diagnosis; some have even received unnecessary operation. Here the clinical features of nine cases are presented. METHODS: Nine patients with AIP were diagnosed and treated at this hospital during the period for 1986 to 1993. The medical records of these patients were reviewed, and diagnosis of AIP in all cases was confirmed by positive Watson-Schwartz test. In three cases, further confirmation was done with erythrocyte porphobilinogen (PBG) deaminase activity measurement. Patients with photosensitivity were excluded. RESULTS: All patients presented initially with abdominal pain; two had been operated upon for acute abdomen. Neurological presentations at diagnosis were motor and/or sensory polyneuropathy (6/9), autonomic dysfunction (6/9), mental change (5/9) and seizure (4/9). Two cases had hyponatremia. One patient died of intractable seizures. CONCLUSIONS: AIP is a frequently forgotten old disease; if not correctly recognized, repeated and unnecessary surgery may occur. However, the diagnosis is easy when the possibility of this disorder is kept in mind.

Cerebrospinal fluid interleukin-6, prostaglandin E2 and autoantibodies in patients with neuropsychiatric systemic lupus erythematosus and central nervous system infections.

Cerebrospinal fluid (CSF) from patients with a variety of central nervous system (CNS) disorders was assayed for cytokines, prostaglandins, and autoantibodies. CSF interleukin-6 (IL-6) in patients with CNS infection (374.24 +/- 92.61 pg/mL) and neuropsychiatric systemic lupus erythematosus (NP-SLE) (71.40 +/- 5.89 pg/mL) were significantly higher than in patients with CNS inflammation (33.92 +/- 29.36 pg/mL) or controls (non-inflammatory CNS diseases) (4.35 +/- 3.00 pg/mL). Interleukin-1 beta, interferon alpha, and tumor necrosis factor alpha were undetectable in these samples: CSF prostaglandin E2 (PGE2) also exhibited similar patterns as IL-6. CSF immunoglobulin G (IgG) in patients with NP-SLE (8.84 +/- 1.80 mg/dL) was much higher than in patients with CNS infection (4.65 +/- 3.09 mg/dL), CNS inflammation (2.54 +/- 1.24 mg/dL), or controls (2.11 +/- 1.03 mg/dL). CSF autoantibodies against calf thymus antigens were present in patients with NP-SLE but not in patients with CNS infection as demonstrated by immunoblot. These results suggest that high IL-6 and PGE2 in CSF favors the diagnosis of CNS infection, while modestly elevated IL-6, high IgG, and autoantibodies against calf thymus antigens in CSF are the features of NP-SLE.

Types of basilar artery syndrome: clinicoradiologic correlation.

Twenty-two patients with ischemic stroke, as a single event, in the territory of basilar artery (BA) are reported. On the basis of the findings from computerized tomography (CT) and clinico-radiologic features, the authors propose that this heterogeneous entity--the basilar artery (BA) syndrome--can be divided into five subtypes. Type 1 (complete type), characterized by infarctions in the whole territory of BA, is incompatible with life; type 2, with extensive brain stem infarct, may result in a locked-in state; and type 3, with infarctions in part of the BA territory (incomplete form or "partial syndrome") may have a more variable clinical outcome. However, type 4, with a top of the BA syndrome, and type 5, with negative CT BA syndrome (angiographically verified), are often more benign. Although initial CT scanning may infrequently be unrevealing, serial and follow-up CT scannings have proven their usefulness in the majority of cases as a noninvasive tool, in contrast to cerebral angiography, for predicting the short-term prognosis of BA syndrome.

Gait disorders of multi-infarct dementia. CT and clinical correlation.

Twenty-five patients with various types of gait disorders of multi-infarct dementia (MID) were reported. The types of gait disorders consisted of lower body parkinsonism (LBP) plus ataxia (6 patients), LBP plus apraxia (5 patients), and a combination of LBP plus ataxia and apraxia (14 patients). Hypertension occurred in 23 (92%) of the 25 patients. Nevertheless, individual stroke risk factors and the locations of infarcts were not significantly different between the subgroups. Ventriculomegaly and "leuko-araiosis" as demonstrated by computed tomography occurred in more than 80% of patients in each subgroup. Atrophy of the superior vermis was seen in 16 (80%) of 20 patients with ataxia as compared to 2 (40%) of the 5 patients without ataxia (p < 0.005). These data suggest that LBP and apraxia of MID were probably determined by the presence of ventriculomegaly or leuko-araiosis or both, and the presence of ataxic component of gait disorder most probably indicates the presence of vermian atrophy.

A case of Hallervorden-Spatz syndrome diagnosed antemortemly.

A sporadic case of Hallervorden-Spatz Syndrome was diagnosed before death. The diagnosis was made on clinical manifestations and histopathology of the tissue fragments obtained from the globus pallidus by stereotaxic brain biopsy. The involvement of thoracolumbar spinal cord is discussed. The cranial computed tomography showed caudate atrophy with bicaudate index (CC/OTcc) of 0.2, and the quotient FH/CC of 1.43, which were indistinguishable from Huntington's disease.

Large vessel disease in Chinese patients with capsular infarcts and prior ipsilateral transient ischaemia.

Carotid angiography was carried out in 21 Chinese patients with acute capsular infarcts; all had had a previous ipsilateral transient ischaemic attack (TIA) or reversible ischaemic neurological deficit (RIND) during the preceding 6 months. Sixteen (group 1) showed lacunar capsular infarcts, and 5 (group 2) either "giant lacunae" or "striatocapsular infarcts". Angiography showed that 81% of group 1 and all group 2 patients had ipsilateral severe stenosis or occlusion of either the M1 segment of the middle cerebral artery or the internal carotid artery. Ten group 1 patients and 3 group 2 patients also had contralateral intra- or extracranial carotid artery stenosis. Apart from hypertension, other risk factors such as hyperfibrinogenaemia, polycythaemia, and low HDL-cholesterol level seem to play a role. Haemorheological abnormalities in the presence of atherostenosis at the orifice of lenticulostriate arteries and/or artery-to-artery embolism might be the cause of infarcts in the majority of the patients. A fifth of patients had recurrent large ipsilateral infarcts. Thus capsular lacunar syndromes with prior ipsilateral TIA or RIND are not as benign as previously thought, and they should indicate more intensive studies including cerebral angiography, and more vigorous therapy.

Multi-infarct progressive supranuclear palsy--case report.

A patient with supranuclear upward gaze palsy, pseudobulbar palsy, dementia, asymmetrical pyramidal signs, and atypical parkinsonism that developed after recurrent strokes was reported. The clinical features closely resembled idiopathic progressive supranuclear palsy (PSP). Computerised tomography of the brain showed, in addition to dilated third ventricle and prominent quadrigeminal plate and ambient cisterns, multiple infarcts at the thalamus, striatum, frontal subcortex and corona radiata. Multi-infarct PSP (MI-PSP) was thought to be the most likely diagnosis rather than coincidental idiopathic PSP with recurrent cerebral infarcts.

The POEMS syndrome among Chinese: association with Castleman's disease and some immunological abnormalities.

POEMS or Crow-Fukase syndrome is a multisystemic, clinically malignant disorder of obscure etiology. Peripheral neuropathy and plasma cell dyscrasia are central features. The authors now report 7 Chinese patients with this syndrome in which PCD or paraproteinemia were absent in 6, and 2 had a lymph node histology resembling that of hyaline-vascular Castleman's disease. Immunological abnormalities consisted of either increased or decreased numbers of B- and T-cells in 2 cases, and an elevated OKT4/OKT8 ratio with paradoxical dissociation of the lymphocyte transformations to various concentrations and types of mitogens in 1 case. This suggests that the underlying abnormalities of POEMS syndrome are heterogeneous and that it may be an immunologically related syndrome of varying etiology.

Paradoxical enlargement of intracranial tuberculomas during treatment of tuberculous meningitis: report of a case.

We report a case of a 32-year-old man who showed paradoxical enlargement of pathologically verified intracranial tuberculomas during a course of adequate antituberculous chemotherapy. Serial computed tomographic scans of the brain disclosed this uncommon phenomenon. Total excision of the lesions with concomitant four-combined antituberculous therapy proved successful. Although the mechanism of this paradoxical phenomenon is not well understood, a defective local tissue immune response with gradually increasing maturity of the lesions during antituberculous therapy, which results in poor penetration of these drugs into the lesions, might be a possible explanation.