Neurologic correlates of osteogenesis imperfecta

The neurologic status of ten patients with osteogenesis imperfecta (OI) was evaluated. Four patients with mild OI (type I) had normal neurologic findings and normal computed tomographic scans. Three of these four patients had macrocephaly. All six patients with severe OI (type III) had cortical atrophy on computed tomographic scan and three were also macrocephalic.     

Multifocal central nervous system damage caused by toluene abuse

Four toluene abusers had evidence of severe multifocal central nervous system damage. Impairment of cognitive, cerebellar, brainstem, auditory, and pyramidal tract function, as well as CT evidence of cerebral cortical, cerebellar, and brainstem atrophy, have been noted. In addition, we found opsoclonus, ocular flutter, and ocular dysmetria. All three patients tested had abnormal brainstem auditory evoked potentials, indicative of brainstem dysfunction. The patient with opsoclonus had CT evidence of brainstem, cerebellar, and cerebral cortical atrophy.     

Auditory brain stem responses in chronic alcoholic patients

Auditory brain stem responses (ABRs) were obtained from 66 chronic alcoholic patients. Forty-one percent of the patients had abnormal ABR indicated by prolonged interwave intervals. The incidence of brain stem abnormalities was related to age, the type and number of alcoholic neurological complications, and cerebral atrophy in computerized tomographic (CT) scan. There was a progressive increase in the incidence of abnormal ABRs with age and the number of alcoholic neurological diseases. Among the neurological complications of alcoholism, patients with cerebellar degeneration had the highest incidence of abnormal ABRs (83%). There was a high correlation between cerebral atrophy in CT scan and abnormal ABRs. The data suggest that laboratory methods such as the ABR and CT scan are useful in evaluating the extent of CNS abnormalities in alcoholic patients.     

Progressive multifocal leukoencephalopathy in a patient with acquired immune deficiency syndrome

Progressive multifocal leukoencephalopathy (PML) occurred in a heterosexual Haitian man with acquired immune deficiency syndrome (AIDS). The patient initially had focal neurologic signs and nonenhancing lesions on a computed tomographic scan. Although PML is rare, it should be included in the differential diagnosis of opportunistic infections associated with AIDS. Brain biopsy is suggested in patients suspected of having PML who might benefit from antiviral therapy.     

Central nervous system involvement in nephropathic cystinosis

Nephropathic cystinosis, an autosomal recessive lysosomal storage disorder due to impaired cystine transport, causes damage to multiple organs that results in end-stage renal disease, hypothyroidism, and retinopathy, usually in childhood. Dialysis and renal transplantation now frequently enable patients with cystinosis to live into adulthood. Examinations at autopsy of a 28-year-old man who died of complications of this disease showed deposits of cystine crystals in multiple organs. There was severe cerebral involvement with multifocal cystic necrosis, dystrophic calcification, spongy change, and vacuolization that had produced profound neurologic deficits. Electron microscopy of the brain documented cytoplasmic deposition of cystine crystals in membrane bound vacuoles within the cytoplasm of pericytes and within parenchymal cells of the white matter. While affected patients who have received renal transplants may no longer die from renal failure, serious, potentially life-threatening, neurologic complications of this disorder may supervene.     

Cerebellar hemorrhage in the term neonate: Developmental and neurologic outcome

To elucidate the effects of cerebellar hemorrhage on the term neonate, neurodevelopmental assessments were conducted at a mean age of 32 months on six children. In addition to cerebellar hemorrhage, ventriculomegaly was present on each subject's initial computed tomographic scan. All were managed without surgical evacuation. Two patients required shunts for progressive ventriculomegaly. Five patients had follow-up computed tomography indicating mild atrophy of the superior anterior vermis of the cerebellum; however, none had abnormal ventricular size or abnormalities of the cerebrum. On detailed examination conducted between the ages of 18 and 48 months, five had hypotonia, truncal ataxia, and intention tremor; two had nystagmus. Only one patient walked independently. Intellectual performance of four patients was within the retarded range and two had mildly delayed development. Two patients had markedly disordered expressive language. These data suggest that term neonates surviving cerebellar hemorrhage have neurologic deficits related to the site of hemorrhage, and cognitive deficits related to more generalized cerebral insult.     

Computerized tomography in hereditary nonprogressive chorea.

A 56-year-old woman had a 50-year history of childhood-onset chorea without progressive neurologic deficit. The patient's father had a lifelong extrapyramidal disorder characterized by a head-nodding tremor and involuntary movements especially evident with anxiety. The computerized tomographic scan was normal, without evidence of cortical or caudate atrophy. The computerized tomographic scan supports the notion of a functional rather than a structural lesion, and may aid in the discrimination of hereditary nonprogressive chorea from more devastating forms of hereditary chorea.     

Computed tomography in subacute sclerosing panencephalitis: report of 15 cases

Computerized tomographic (CT) study of the brain was performed in 15 cases of subacute sclerosing panencephalitis (SSPE). Most patients in Stage II (6/8) had cerebral edema and diffuse white matter low attenuation, and patients in Stages III and IV (5/7) had atrophy of cerebral cortex, brainstem and cerebellum. Low density areas in deep grey matter nuclei (5 cases), large focal areas of white matter hypodensity (3/15) and evidence of brainstem atrophy without cerebral atrophy (2/15) were features not hitherto described. One patient in Stage III had normal scan. Correlation of scan findings was better with the stage of the disease than with the duration of SSPE.     

Computed tomography (CT) in late infantile metachromatic leucodystrophy

Computed tomographic features of 7 cases of the late infantile form of MLD confirmed by sural nerve biopsy are presented. Diffuse symmetrical white matter, low attenuation of the cerebral parenchyma was the common feature. Hypodensity of the temporal lobes and the cerebellar hemispheres are 2 features which have not been reported earlier. Three patients had brainstem atrophy without evidence of cerebral atrophy. Awareness of the various CT features of MLD may help in more definitive radiological diagnosis of the disease and to differentiate it from other dysmyelinating diseases of the central nervous system.     

Multifocal central nervous system lesions in three patients with trichinosis

Three patients with trichinosis developed central nervous system complications. Cerebral computed tomography showed multifocal hypodense lesions in two patients. The lesions were associated with contrast enhancement and cortical gyral enhancement in the first case, suggesting hypoxia and infarction. In the second patient, magnetic resonance imaging showed multiple high-signal-intensity lesions. Early cerebral computed tomography was normal in the third patient. All patients recovered after treatment with antiparasitic drugs and corticosteroids. We suggest that neurologic complications of trichinosis should be treated by corticosteroids and flubendazole.     

Progressive multifocal leukoencephalopathy: clinical and radiographic features

Between April 1982 and March 1984 7 pathologically confirmed cases of progressive multifocal leukoencephalopathy (PML) were diagnosed at our institution. Only 1 case had been seen in the preceding twenty years. Four patients had acquired immunodeficiency syndrome (AIDS). The others had chronic lymphocytic leukemia, Hodgkin's lymphoma, and systemic lupus erythematosus. All patients presented with progressive neurological deficits. In most, the initial computed tomographic (CT) scan was disproportionately less abnormal than the clinical findings. In 5 patients the first CT scan revealed hypodensities of the cerebral white matter which lacked mass effect and did not enhance with contrast agent. The lesions were observed to enlarge progressively on CT scans but often lagged behind the rate of clinical evolution. Although 3 patients were treated with cytosine arabinoside, none improved. PML had similar clinical, radiographic, and pathological features in the AIDS and non-AIDs patients. Of 79 AIDS patients cared for at our institution between December 1979 and December 1983, 3.8% had PML. PML should be suspected in AIDS patients in the presence of the characteristic CT features, especially when CT-clinical dissociation occurs.     

Lissencephaly-pachygyria associated with congenital cytomegalovirus infection.

We report the presence of major cerebral migrational defects in five severely, multiply handicapped children with congenital cytomegalovirus (CMV) infection. These patients had both computed tomographic (CT) scan and magnetic resonance imaging (MRI) evidence of marked migrational central nervous system defects consistent anatomically with the spectrum of lissencephaly-pachygyria, a disorder commonly idiopathic or associated with chromosomal abnormalities or with unknown early gestational insults. Neuroradiologic features included broad, flat gyri, shallow sulci, incomplete opercularization, ventriculomegaly, periventricular calcifications, and white-matter hypodensity on CT scans or increased signal intensity on long-TR MRI scans. Evidence for congenital CMV infection included prenatal onset of microcephaly, periventricular calcifications, neonatal jaundice, hepatomegaly, elevated CMV-specific immunoglobulin M, or viral isolation from urine. Previous reports of the neurologic sequelae of CMV have emphasized varying degrees of psychomotor retardation, cerebral palsy and epilepsy due to polymicrogyria, periventricular calcification, microcephaly, or rarely, hydrocephalus. Our patients appear to represent extremely severe examples of the effects of CMV on neurologic growth, maturation, and development. Recognition of these severe migrational abnormalities was improved by use of MRI, a technique that affords superior definition of the nature and extent of gyral and white-matter abnormalities. We suggest that these abnormalities may be more common than has previously been recognized.     

Central pontine and extrapontine myelinolysis owing to disequilibrium syndrome

Neurologic disorders can be seen in patients with end-stage renal failure owing to complications of hemodialysis or peritoneal dialysis. The disequilibrium syndrome can be seen, usually soon after or toward the end of dialysis. We report a patient with central pontine and extrapontine myelinolysis owing to disequilibrium syndrome. The patient had depressed consciousness, agitation, tremor, stupor and hyperactive deep tendon reflexes toward the end of the second peritoneal dialysis. A brain computed tomographic (CT) scan showed hypodense lesions in pontine and extrapontine locations without radiocontrast medium enhancement After 2 days, the patient had only minimal memory deficits. A control brain CT scan 1 week later showed a decrease of the lesions in central pontine and extrapontine locations. Central pontine and extrapontine myelinolysis should be suspected and investigated in the acute neurologic disorders of dialysis patients.     

Prothrombotic states in HIV disease and stroke complications

Thirty to 40% of patients with acquired immunodeficiency syndrome (AIDS) have symptoms and signs of neurologic dysfunction. Radiographic and pathologic studies reveal evidence of neurologic involvement in 75% to 90% of cases of advanced-stage human immunodeficiency virus-1 (HIV) disease. Before the introduction of highly active antiretroviral therapies, AIDS dementia complex and opportunistic infections of the central nervous system were frequent causes of global cerebral dysfunction. Focal neurological deficits were most commonly due to toxoplasmosis, primary central nervous system (CNS) lymphoma, or progressive multifocal leukoencephalopathy.Thrombotic events including cerebral infarction and venous thrombosis have been reported in patients with HIV/AIDS. Various hematologic abnormalities have been described that could lead to a hypercoagulable state, including antiphospholipid antibodies; deficiencies of antithrombin III, protein C, and protein S; and increased levels of von Willebrand factor and D-dimer.In the majority of cases of cerebral infarction, there is an associated precipitating event such as opportunistic infection or malignancy. However, vasculopathy has also been described in both adults and children. Furthermore, there are reports of HIV patients with cerebral infarction in whom an HIV-related coagulopathy is identified and other cases where no explanation is found, but only a limited hematologic evaluation has been performed.     

The encephalopathy of sepsis

Twelve fatal cases of encephalopathy associated with sepsis were examined in a ten-year retrospective study. The sources of infection and organisms isolated were variable. Six of the patients had focal neurologic signs; five had seizures. The level of consciousness varied from drowsiness to deep coma, and electroencephalograms revealed diffuse or multifocal abnormalities. Computed tomographic head scans and cerebrospinal fluid examinations were usually unremarkable. Eight patients had disseminated microabscesses in the brain at autopsy. Four patients had proliferation of astrocytes and microglia in the cerebral cortex, a feature associated with metabolic encephalopathies. Additional findings included cerebral infarcts, brain purpura, multiple small white matter hemorrhages, and central pontine myelinolysis. Although sepsis may cause encephalopathy by producing disturbances in cerebral synaptic transmission and cerebral energy production through a toxic mechanism, bacterial invasion of the brain with the formation of disseminated microabscesses is also an important cause.     

Heterogeneity of classic congenital muscular dystrophy with involvement of the central nervous system: report of five atypical cases

A heterogeneous group of patients with congenital muscular dystrophy associated with clinical or radiologic central nervous system involvement other than the severe classic form with merosin deficiency, muscle-eye-brain disease, and Walker-Warburg syndrome is described. A probable hereditary or familial occurrence could be suggested in all patients. One merosin-positive patient presented severe motor incapacity and cerebral atrophy without any clinical manifestation of central nervous system involvement. A second patient, also merosin-positive, had moderate motor and mental handicap, and epilepsy with no changes in neuroimaging. A third patient, found to have partial merosin deficiency by muscle biopsy, manifested severe psychomotor retardation and cerebral atrophy with foci of abnormal white-matter signal on magnetic resonance imaging. Finally, two merosin-positive siblings with microcephaly, mental retardation, and an incapacitating progressive neuromuscular course, exhibited cataracts without defects of neuronal migration or brain malformation. This report emphasizes the broad clinical spectrum and heterogeneity of merosin-positive congenital muscular dystrophy with associated central nervous system involvement, and illustrates the importance of further studies on clinical, immunohistochemical, and genetic grounds for identifying new subsets of congenital muscular dystrophy.     

Persistent vegetative state. Extension of the syndrome to include chronic disorders

Twenty-nine institutionalized patients had the vegetative state as a sequela of chronic progressive neurologic disorders. During three years, the state was persistent; none improved, ten died. Eight similar patients were reviewed retrospectively post mortem. Eight patients with severe dementia, while acutely ill or sedated, temporarily met the criteria for persistent vegetative state (PVS) but improved when the underlying condition was treated. Abnormalities on electroencephalography or computed tomographic scan are not specific for the PVS. Electroencephalograms were normal in three patients with PVS. The computed tomographic scans showed extensive destruction of the brain parenchyma but were not different from those of severely demented patients without the PVS. The PVS is a feature of the terminal phase of several progressive neurologic disorders. Patients should be treated without excessive intervention.     

Cerebrovascular lesions and livedo reticularis (Sneddon's syndrome) — a progressive cerebrovascular disorder?

Summary Four cases are described in which livedo reticularis was associated with repeated cerebrovascular accidents, which eventually resulted in severe disability in two cases. Patients with severe disability had a history of many years, whereas two patients with little or moderate residual disability had a follow-up of 3 years each. CT scan revealed multifocal cerebral infarctions and cortical atrophy in all cases. Repeated cerebral angiograms, done in three cases, showed no signs of a vascular disease. There were no parameters that pointed to active immunological or inflammatory disorder. Neither clinical evidence of heart or large vessel disease was found. Observations suggest that a so-far unknown progressive cerebral vessel disease associated with livedo is the cause of a steady increase in multiple small cerebral infarctions. Because of the progressive character of the disease the search for effective therapy is needed.     

Globoid cell leukodystrophy: cranial computed tomography and evoked potentials

The evoked potentials and cranial computed tomographic (CT) scan findings in a case of early infantile globoid cell leukodystrophy are presented. The brain stem auditory evoked responses (BAERs) and the flash visual evoked potentials (VEPs) were abnormal. Repeated cranial CT scans showed multiple areas of increased attenuation and progressive cerebral atrophy. These evoked potential and CT scan patterns occurring concomitantly in an infant are suggestive of globoid cell leukodystrophy.     

PATHOLOGY OF THE CENTRAL NERVOUS SYSTEM IN 40 CASES OF ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS)

The central nervous system was examined in 40 AIDS patients who died between August 1982 and 1987. The cases included two children born to intravenous drug abusers and 38 male adults. The brains of eight patients who had no clinical or radiological evidence of central nervous system involvement showed non-specific changes which included microglial nodules, perivascular mononuclear cuffs, mineralization of blood vessels and granular ependymitis. In 32 brains from patients with neurological symptoms, toxoplasmosis was the most frequent finding (19 cases) manifested by multifocal, necrotic lesions or a diffuse pseudo-encephalitic process. Other opportunistic infections included cytomegalovirus (eight cases), progressive multifocal leucoencephalopathy (two cases), cryptococcosis (one case), aspergillosis (one case), multiple bacterial microabscesses (one case) and Mycobacterium avium intracellulare (one case). Two patients had cerebral lymphoma. Subacute encephalitis with white matter lesions and multinucleated giant cells characteristic of HIV infection was present in 15 cases. Various combinations of all these infections were encountered in the same brain, sometimes in the same area and, occasionally, in the same cell.