Spinal cord calcification in an early-onset progressive leukoencephalopathy

Spinal cord calcifications are an unusual finding in pediatric neurology. We here describe a young child who presented severe psychomotor delay, tetraplegia, deafness, and anemia. Neuroradiological investigations revealed severe leukodystrophy and unusual calcifications in the cerebral white matter and all along the medullary pathways. Common infectious and metabolic diseases were ruled out. A mild reduction in the activity of several respiratory chain complexes was documented on muscle biopsy. Of interest, we found an intronic variant in DARS2, a gene involved in mitochondrial DNA translation, responsible for the syndrome of leukoencephalopathy with brainstem and spinal cord involvement and high brain lactate. In our opinion, our case, and probably 2 previously reported Japanese siblings with a picture very similar to that of our patient, could represent a new, progressive leukoencephalomyelopathy.     

Reversible diffuse white matter lesion in Alagille syndrome

A boy with genetically confirmed Alagille syndrome was incidentally found to manifest striking diffuse hyperintensity of the white matter on T₂-weighted cranial magnetic resonance images. He never exhibited signs of hepatic encephalopathy. For his progressive liver failure, he underwent a live-donor liver transplant at age 2 years, which unexpectedly resulted in a near-complete resolution of the diffuse white matter lesion. Reversible white matter lesions attributed to cerebral edema were reported in adult patients with liver cirrhosis, but not in the pediatric population. The diffuse reversible white matter lesion in the present case demonstrated T₂ hyperintensity, coupled with restricted diffusion confirmed by apparent diffusion coefficient, and was suggestive of etiologies such as ischemia or cytotoxic edema rather than vasogenic edema.     

Dichotic Listening Performances of Patients with Chronic Exposure to Organic Solvents

The present study was concerned with the clinical utility of dichotic listening in the examination of individuals with “intermediate” levels of organic solvent exposure (i.e., exposure sufficient to cause peripheral neurological symptoms and mental status complaints, but not manifest solvent encephalopathy). Neuropathological studies on animals and humans have indicated that organic solvents often caused injury to subcortical white matter. Because other studies involving patients with relatively specific white matter disease have found these patients to be impaired in dichotic listening, it seemed logical to investigate dichotic listening in solvent-exposed workers. Among solvent-exposed workers, dichotic listening was frequently impaired in relation to previously established norms or a control group matched for age, education, and stability of employment. Dichotic listening proved far more sensitive than other neuropsychological measures administered. Results have implications for both the neuropsychological assessment of solvent-exposed patients and for the pathophysiology of multiple ''peak exposures'' to organic solvents in humans.     

Tuberculous meningitis masked by delirium in an alcohol-dependent patient: a case report

OBJECTIVE: Patients with alcohol dependence syndrome can present with delirium which will mask underlying organic causes for the delirium. However, other medical diseases can also present with similar symptoms and should not be missed. The issues related to differentiating the different causes of delirium are briefly discussed. We describe a case of tuberculous meningitis in a patient with history of alcohol dependence who presented with delirium. METHOD: A case report. RESULTS: A 38-year-old male was admitted with history of irrelevant talk and abnormal behaviour of 2-month duration. He was also disoriented and his short-term memory was impaired. He reported visual hallucinations. He had history of alcohol dependence of 5 years. A detailed mental status examination and neurological workup revealed an organic psychosis. CT scan showed a hypodense lesion suggestive of a tuberculoma. The cerebrospinal fluid findings were corroborative. He responded to antituberculous drugs which he took for one and a half years and recovered completely. He also underwent group therapy for his alcohol dependence and has since then refrained from alcohol intake. Currently he has gone back to his work as a car mechanic. CONCLUSION: We have highlighted the need for diagnosing and investigating carefully the cause of delirium in a patient with alcohol dependence syndrome. This shows that other curable causes of delirium must also be investigated in patients with alcohol dependence.     

Nonfluent aphasia in a patient with Waldenstrom's macroglobulinemia.

Waldenstrom's macroglobulinemia (WM) is an uncommon low-grade lymphoma. Cognitive impairment due to central nervous system infiltration by lymphoplasmocytoid cells (Bing-Neel syndrome) has been rarely reported. We describe a 54-year-old man who was referred to a memory disorder clinic with a 9-month history of clinically obvious nonfluent aphasia and WM. He underwent extensive neuropsychological testing, clinical examination and structural and functional brain imaging. The diagnosis of the diffuse form of the Bing-Neel syndrome was supported by abnormal lymphoid cells found in the cerebrospinal fluid. Structural and functional brain imaging revealed impairment of brain areas due to white matter changes and subsequent functional deficits mimicking the neuropsychological syndrome encountered in progressive nonfluent aphasia. The diffuse form of Bing-Neel syndrome and neurological deficits are assumed to be the result of leptomeningeal infiltration by malignant cells and/or neoplastic vascular obstruction.     

Central nervous system vasculitis in cytomegalovirus infection

A 51-year-old man received cyclophosphamide, vincristine, procarbazine and prednisone in the treatment of a small-cell undifferentiated lymphoma. Two years later, he developed a rapidly progressive neurological syndrome characterized by a decline in alertness, deafness, blindness and paraplegia. Examination of his eyes revealed severe hemorrhagic chorioretinitis. Leg weakness was thought to be due to transverse myelopathy at a thoracic level. He had a grand mal convulsion and died from terminal bronchopneumonia.Autopsy examination of the eyes revealed sweeping destruction of the retina due to inclusion body chorioretinitis. The brain and spinal cord showed multiple small infarcts accounting for the deafness and paraplegia. The lesions were due to occlusive arteritis in gray and white matter. Veins were also involved.Tissue surrounding the foci of necrosis contained cells with intranuclear and intracytoplasmic inclusion bodies. Some of the Cowdry type A inclusion bodies were large, measuring 30 μm in diameter and were located in enlarged cells.Electron microscopy of retina and brain tissue disclosed virus particles compatible with cytomegalovirus.The subject of cerebral and ocular angiitis due to herpes virus infections is reviewed.     

A case of hemimegalencephaly with slowly progressive expansion

We report a case of a male infant with refractory epilepsy, demonstrating hemimegalencephaly with slowly progressive expansion. The patient experienced his first seizure at 4 months of age. Subsequently, tonic seizures occurred very frequently despite extensive antiepileptic medications, and his development deteriorated. Cranial magnetic resonance imaging (MRI) at 4 months of age showed focal cortical dysplasia in the right opercular area. This focal lesion gradually expanded, and became thickened. Five years later, the dysplastic lesion occupied most of the right cerebral hemisphere and the volume of the right hemisphere increased, indicating hemimegalencephaly. He had profound motor and intellectual retardation. In the abnormal cerebral hemisphere, fluorodeoxyglucose-positron emission tomography (FDG-PET) showed marked hypometabolism, and ictal single photon emission computed tomography (SPECT) showed hyperperfusion, more pronounced in the right frontal area. These findings are consistent with a hemimegalencephaly. Hemimegalencephaly with such a progressive expansion has never been described previously. These findings are consistent with a hemimegalencephaly showing progressive expansion, which has never been described previously.     

Parkinsonism, pyramidal signs, polyneuropathy, and cognitive decline after long-term occupational solvent exposure

It is well known that exposure to manganese, solvents, or carbon monoxide in an occupational setting may lead to central nervous system damage and parkinsonism. The most important solvents in this respect are methanol, toluene, carbon disulfide, and n-hexane. We describe three patients who had been exposed to various solvents for more than 20 years (25, 34, and 46 years). They presented with parkinsonism, pyramidal signs, mild cognitive decline, and unresponsiveness to levodopa. Two patients had a predominantly axonal and sensory polyneuropathy of the lower legs with fasciculations in one of them. Parkinsonian features were progressive, even after the patients had stopped work. We present clinical data, neuropsychological findings, and results of brain computed tomography or magnetic resonance imaging, electroneuromyography, evoked potentials, single photon emission computed tomography, and positron-emission tomography. There is growing evidence that various organic solvents give rise to a parkinsonism syndrome with pyramidal features in susceptible individuals. Received: 22 December 1997 Receibed in revised form: 17 July 1998 Accepted 21 July 1998     

职业性有机溶剂中毒15例临床表现和影像学特征分析

目的 探讨职业性有机溶剂中毒的临床表现、神经影像学特征、治疗及预后。方法 回顾性分析15例职业性有机溶剂中毒患者的临床资料。结果 15例患者均急性或亚急性起病,有明确的有机溶剂职业接触史,主要临床表现包括头晕(73.3%)、认知功能下降(60%)、锥体束损害(53.3%)、颅内高压综合征(46.7%)、意识障碍(33.3%); 其中14例患者头颅磁共振成像(Magnetic resonance imaging,MRI)显示为弥漫性脑组织肿胀,以双侧大脑半球白质为主,呈“火焰状”,10例累及双侧基底节(苍白球),8例累及双侧小脑齿状核,呈“肾形”改变,5例累及双侧丘脑; 所有患者使用脱水剂、糖皮质激素及高压氧等综合治疗后,其中12例患者好转出院,无或仅遗留轻微后遗症,3例患者无明显改善,预后差。结论 职业性有机溶剂中毒以头晕、认知功能下降、锥体束损害、颅内高压综合征及意识障碍等中毒性脑病表现为主,典型头颅MRI为双侧大脑半球白质、苍白球及小脑齿状核对称性病变,结合患者职业接触史需考虑本病; 早期、长程、足量给予脱水剂、糖皮质激素及高压氧等综合治疗,大多数患者预后良好。     

Cerebellar ataxia with hypogonadotropic hypogonadism]

A 38-year-old male began to develop progressive difficulty in speaking and walking in his early thirties. He was the younger of four siblings from the parents of consanguineous marriage. Allegedly, his brother had showed similar symptoms. On examination, he was sexually underdeveloped with absent facial and public hair as well as small firm testes. He showed typical eunuchoid habitus. Neurologically, his gait was markedly ataxic and speech was explosive. He was mildly demented (verbal IQ = 66) and eupholic. Generalized hyperreflexia and positive Babinski were observed. There were no signs of extrapyramidal, autonomic or peripheral nerve involvement. Laboratory data were remarkable for low level of serum gonadotropins and low level of HVA and 5-HIAA in CSF. Plasma long-chain fatty acids were normal and lysosomal enzymes in leukocyte including ASA showed no significant change. EEG showed diffuse slow activities with spikes on photic stimulation. The endocrinological studies including insulin-induced hypoglycemia and TRH test demonstrated hypothalamus-pituitary axis dysfunction. GH-RH test showed delayed response of GH secretion, suggesting the presence of hypothalamic disturbance. Brain CT showed cerebellar atrophy and symmetrical low density area in the cerebral white matter. On MRI, T2 weighed image showed diffuse and symmetrical high intensity area in the cerebral white matter. High signal intensities were also noted in the bilateral thalamus and pons. It is suggested that both hypogonadotropic hypogonadism and cerebellar ataxia in this disease may have a common underlying pathology of white matter.     

Chronic painters''syndrome

Seventy house painters were examined after being referred because organic solvent intoxication of dementia was suspected. In 50 cases no competitive etiological factors to the cerebral symptoms other than exposure to organic solvents could be disclosed. In these, neuropsychological examination showed signs of intellectual impairment in 39 patients and neuroradiological examination by PEG or CT demonstrated the presence of cerebral atrophy in 31 patients; 38 patients studied with CT were compaired to an age-matched control group regarding maximum sulcus width, and a highly significant difference was found. It is argued that long-term exposure to turpentine substitute-often through a period with acute intoxication symptoms--gradually may lead to the development of a chronic brain syndrome, which we have called the "chronic painters' syndrome".     

An 81-year-old man with personality change, dementia, and gait disturbance with diffuse leukoaraiosis of the cerebral white matter]

We report an 81-year-old patient with progressive dementia, disinhibition, and gait disturbance. He showed visuospacial disorientation, apathy, and gait disturbance at 76 years of age. When he was 77 years old, he was diagnosed Parkinson's disease and treated with the 1-dopa, the dopamine agonist, the amantadin, and the anti-cholinergic drug. These treatments didn't improve his motor disturbances. His motor disturbances, apathy, and abnormal behavior progressed gradually. He was admitted to the hospital at the age of 77. He was severely demented and akinetic. Sometime, violent behavior and hallucination were seen. The brain MRI showed frontotemporal lobe atrophy and severe leukoaraiosis of the frontal white matter. At 79 years of age, he became mute and bedridden. When he was 80 years old, large infarction occurred in his occipital lobe. He died due to renal failure and respiratory suppression at 81 years of age. His brain was examined pathologically. At the neurological CPC, the chief discussant arrived at the conclusion that his diagnosis was Binswanger's disease. Other possibilities discussed were FTD, CBD, and progressive subcortical gliosis. The post-mortem examination revealed diffuse white matter degeneration due to atherosclerotic change of the small artery, many lacunar infarctions, and severe infarction of the occipital lobe. These findings led the diagnosis of Binswanger's disease and cerebral infarction.     

Posttraumatic mid-facial pain and Meige's syndrome relieved by pressure on the nasion and retrocollis

A 42-year-old farmer developed persistent mid-facial segmental pain and Meige's syndrome several months after suffering facial trauma and a fracture of the nose. He was not afflicted by systemic ailments, had no family history of movement disorder and no history of exposure to neuroleptic drugs. He was capable of suppressing his facial pain by performing a ritual that included forcefully tilting his head backwards, lowering of his eyelids and applying strong pressure to his nasion. Exceptionally dystonic movements and elaborate behavioral rituals may serve as a mechanism of pain suppression.     

A patient with myopathy due to preclinical Cushing syndrome]

A 57 year-old man with a history of diabetes mellitus was admitted to our hospital for the complaint of slowly progressive muscle weakness involving proximal limbs and head dropping. His serum CK level was within normal range, and muscle biopsy showed no inflammatory changes. To rule out myasthenia gravis, computerized tomography was done for the detection of thymoma, and detected an adrenal tumor in stead. He was not over-weighted, and his morning plasma levels of ACTH and cortisol were within normal ranges. Additional hormonal examinations revealed daily autonomous hypersecretion of cortisol. He received diagnosis of preclinical Cushing syndrome. After resection of the tumor, muscle weakness improved and his diabetes mellitus was controlled better. The muscle symptoms seem to be related with steroid myopathy. Preclinical Cushing syndrome should be included as a differential diagnosis for myopathy of unknown etiology.     

Isaacs' syndrome: clinical and electrophysiological response to gabapentin

A patient with Isaacs' syndrome had generalized muscle spasms, twitching, and progressive muscle stiffness for 21 years. Electrodiagnostic study showed continuous spontaneous motor-unit activity and the presence of M-wave afterdischarges. He responded dramatically to treatment with carbamazepine but developed a drug rash; his treatment was changed to gabapentin with continued improvement. Subsequent nerve conduction studies showed decreased amplitude and later an absence of M-wave afterdischarges. Gabapentin thus appears to be an effective treatment for Isaacs' syndrome.     

An autopsy case of Prader-Labhart-Willi syndrome

An autopsy case of 23-years-old man with Prader-Labhart-Willi syndrome (P-L-W syndrome), who had died by acute renal failure due to burn injury, was reported. P-L-W syndrome was constituted by hypotonia, hypogonadism, hypomentia, obesity and other minor anomalies, however, CNS anomaly had not been reported. The patient sat at 3 years of age, walked at 4 years old, began to utter single words at 3-4 years, and he began to obese at 4 years of age. He fulfilled the condition of P-L-W syndrome mentioned above. On his age 15, laboratory findings on admission revealed remarkable diabetic pattern by oral glucose tolerance test and intelligence quotient was 28, and the other laboratory findings were within normal limit. During his clinical history, complications of diabetes mellitus, such as diabetic retinopathy and neuropathy, were aggrevated, and upstanding and gait were impossible at 20 years of age. On his age 23, he suffered from burn injury at left lower extremity and he fell in acute renal insufficiency. Five autopsy cases of P-L-W syndrome have been reported so far, however, CNS anomaly has not been observed. Following anomalies in our case was recognized, such as shortness of the frontal lobe, partial micropolygyria of the dentate nucleus, heterotopia of the inferior olivary nucleus, ectopia of Purkinje cell in the molecular layer, heterotopia of middle sized neuron in the deep white matter of the cerebellum and large number of residual nerve cells in the cerebral subcortical white matter.(ABSTRACT TRUNCATED AT 250 WORDS)     

A case of combined paraneoplastic neurological syndrome, with Lambert-Eaton myasthenic syndrome manifesting as severe respiratory failure, and anti-Hu syndrome]

A 63-year-old man complained of rapidly progressive respiratory failure, requiring a control respiration. He subsequently, presented with muscle weakness involving the neck and all the extremities, superimposed by painful paresthesia. He was proven to carry small-cell lung cancer (SCLC). Neurophysiological examinations revealed the waxing phenomenon at 30 Hz repetitive motor nerve stimulation. Positive serum autoantibodies were detected to voltage-gated calcium channel and Hu proteins. He received diagnosis of combined Lambert-Eaton myasthenic syndrome (LEMS) and anti-Hu syndrome. The initial chemotherapy for SCC alleviated his respiratory and neurological symptoms. But he developed multiple cranial palsies and fatal respiratory distress two months later. There is only a few reports about LEMS complicated by respiratory failure as an initial presentation. Various clinical manifestations including respiratory failure at the onset could be best explained by the combination of LEMS and anti-Hu syndrome in this case.     

有机溶剂致中毒性脑病5例分析

目的探讨工作环境接触有机溶剂致中毒性脑病患者的临床表现及影像学特点。方法回顾性分析5例在工作环境中接触有机溶剂致中毒性脑病患者临床表现及CT和MRI资料。结果所有患者均有有机溶剂接触史;临床表现以头晕、恶心呕吐、记忆力下降、走路不稳为主要特征;CT均表现为双侧对称边界清楚的低密度病灶,无占位效应。头部MRI表现为双侧对称性长T1长T2信号,Flair呈高信号,增强无强化。结论结合工作环境毒物接触史、中枢神经症状,及CT和MRI表现,可诊断有机溶剂中毒性脑病。     

Canine spongiform leukoencephalomyelopathy is associated with a missense mutation in cytochrome b

Two families of dogs (Australian cattle dogs and Shetland sheepdogs) with an inherited "spongiform leukoencephalomyelopathy" were identified, with widespread vacuolation of white matter of the brain and spinal cord. Affected dogs of both breeds developed tremors at 2-9 weeks of age followed by progressive neurological worsening with ataxia, paresis, paralysis, spasticity, and cranial nerve dysfunction. The modes of inheritance of both families were most likely maternal. The cerebrospinal fluid (CSF) analysis showed elevated ratio of 3-OH butyrate to acetoacetic acid. Mitochondrial DNA sequencing showed a G to A transition at 14,474 nt (G14474A, GenBank accession no. NC002008 ) that results in an amino acid change of valine-98 to methionine (V98M) of mitochondrial encoded cytochrome b. Western blot analysis showed increased levels of core I and core II but decreased level of cytochrome c1 of the complex III and cytochrome c oxidase of the complex IV of the respiratory chain.