Cerebellar Encephalopathy Research Articles

Metronidazole Encephalopathy EEG Features: A Case Report with Systematic Review of the Literature.

Metronidazole-induced encephalopathy (MIE) is a rare and often under-recognized iatrogenic condition. The diagnosis should be considered in metronidazole-treated patients presenting with acute encephalopathy, unprovoked seizures and cerebellar signs. While typical magnetic resonance imaging (MRI) findings strongly support the diagnosis, electroencephalography (EEG) features have been rarely reported and poorly described. We present a longitudinal EEG assessment in one patient with encephalopathy due to metronidazole toxicity who presented a peculiar EEG pattern presentation and evolution. During the acute phase of encephalopathy, the EEG showed a monomorphic, sharply contoured theta activity symmetrically represented over frontal regions with an anterior–posterior progression which evolved in parallel with clinical worsening. Together with a systematic review of the literature, we discuss whether this EEG activity may represent a distinct neurophysiological correlate of ‘cerebellar encephalopathy’.

50 Years Ago in TheJournal ofPediatrics: The Coincidence of Neuroblastoma and Acute Cerebellar Encephalopathy

50 Years Ago in TheJournal ofPediatrics: The Coincidence of Neuroblastoma and Acute Cerebellar Encephalopathy

Hypertensive encephalopathy with obstructive hydrocephalus

We present a 33-year-old man who had hypertensive encephalopathy accompanied by obstructive hydrocephalus. The patient presented with headache subsequent to a hypertensive emergency. MR imaging revealed evidence of brainstem and bilateral cerebellar encephalopathy that resolved completely. Resolution of the cerebellar edema also led to improvement of the hydrocephalus.

Hypertension-Induced Cerebellar Encephalopathy and Hydrocephalus in a Male

Hypertensive encephalopathy is believed to be caused by an abrupt elevation in systemic blood pressure. It rarely occurs in children and can be neurologically devastating if it is not recognized and treated immediately. This report describes an 11-year-old male who presented with edema and a cerebellar lesion, with acute obstructive hydrocephalus resulting from hypertensive encephalopathy. A shunt was inserted to relieve pressure in the acute stage. The patient's hydrocephalus and cerebellar swelling subsided when his blood pressure was controlled. The cerebellar lesion had been initially diagnosed as a glioma. In children, a cerebellar lesion occurring with acute obstructive hydrocephalus and hypertensive encephalopathy is rare but reversible. Clinicians should be aware of this condition because it might be misdiagnosed as a tumor of the posterior fossa.

Comparative observations on inorganic and organic lead neurotoxicity.

Environmental and occupational exposure to lead still generates concern, and recent studies have focused such concern on the role of body burden of lead during the fetal/neonatal period, especially in the genesis of disturbed central nervous system development. This discussion provides some comparative observations on the neurotoxicity of inorganic and organic lead species. The characteristics acute, predominantly cerebellar encephalopathy associated with neonatal high lead exposure contrasts to the subtle, axo-dendritic disorganization shown to be associated with low-level neonatal inorganic Pb2+ exposure. There is a preferential involvement of the hippocampus in both low-level inorganic Pb2+ and organolead exposure, and the clinical syndromes of irritability, hyperactivity, aggression, and seizures are common features of disturbed hippocampal function. Neurotransmitter system abnormalities have been described with inorganic Pb2+, but recent attention has focused on the abnormalities in glutamate, dopamine and/or gamma-aminobutyric acid (GABA) uptake, efflux, and metabolism. Abnormalities of GABA and glutamate metabolism are also found with the organolead species. While the pathogenesis is still unclear, the interactive role of Pb2+ on mitochondrial energy metabolism, Ca2+ uptake, intracellular Ca2+ homeostasis, and neurotransmitter influx/efflux is considered. Consideration is given to low-dose inorganic Pb2+ and organolead effects on mitochondrial and/or plasmalemmal membranes inducing either Cl-/OH- antiport-linked depolarization, inhibition of intracellular ATP biosynthesis and transduction. and/or abnormalities induced due to the preferential affinity of Pb2+ for intracellular Ca2(+)-cytoplasmic protein, e.g. calmodulin. Testable hypotheses are presented that may provide an understanding of the pathogenesis underlying dystrophic neuronal development under the influence of inorganic or organolead intoxication.

Comparative Observations on Inorganic and Organic Lead Neurotoxicity

Environmental and occupational exposure to lead still generates concern, and recent studies have focused such concern on the role of body burden of lead during the fetal/neonatal period, especially in the genesis of disturbed central nervous system development. This discussion provides some comparative observations on the neurotoxicity of inorganic and organic lead species. The characteristics acute, predominantly cerebellar encephalopathy associated with neonatal high lead exposure contrasts to the subtle, axo-dendritic disorganization shown to be associated with low-level neonatal inorganic Pb2+ exposure. There is a preferential involvement of the hippocampus in both low-level inorganic Pb2+ and organolead exposure, and the clinical syndromes of irritability, hyperactivity, aggression, and seizures are common features of disturbed hippocampal function. Neurotransmitter system abnormalities have been described with inorganic Pb2+, but recent attention has focused on the abnormalities in glutamate, dopamine and/or gamma-aminobutyric acid (GABA) uptake, efflux, and metabolism. Abnormalities of GABA and glutamate metabolism are also found with the organolead species. While the pathogenesis is still unclear, the interactive role of Pb2+ on mitochondrial energy metabolism, Ca2+ uptake, intracellular Ca2+ homeostasis, and neurotransmitter influx/efflux is considered. Consideration is given to low-dose inorganic Pb2+ and organolead effects on mitochondrial and/or plasmalemmal membranes inducing either Cl-/OH- antiport-linked depolarization, inhibition of intracellular ATP biosynthesis and transduction. and/or abnormalities induced due to the preferential affinity of Pb2+ for intracellular Ca2(+)-cytoplasmic protein, e.g. calmodulin. Testable hypotheses are presented that may provide an understanding of the pathogenesis underlying dystrophic neuronal development under the influence of inorganic or organolead intoxication.

Clinical outcome in children with acute cerebellar encephalopathy and neuroblastoma.

Acute cerebellar encephalopathy (ACE)--ataxia often associated with opsoclonus, polymyoclonus, and irritability--may be associated with neuroblastoma and should be suspected in a child who presents with ACE. The survival in ten children with ACE associated with neuroblastoma was 100%. Most of the tumors were ganglioneuroblastomas. The abdomen was the most common location for the tumor in this study although it also can be found in the mediastinum. All patients with this syndrome had a localized tumor. With ACTH therapy, ACE may resolve early postoperatively, but it tends to recur in most patients, continuing for as long as 3 years after the initial operation. Treatment with ACTH or prednisone modifies and rapidly clears the symptoms during the acute episode of recurrent ACE as well as helps to resolve subsequent neurologic sequelae. Significant neurologic sequelae persisted in seven of ten patients and included deficits in cognition or intellect, hyperactivity, impulsivity, emotional lability, and mild motor deficits. Seizures were seen in one patient.

Development of resistance to lead encephalopathy during maturation in the rat pup.

The purpose of this study was to determine the maturational period during which the rat pup becomes resistant to the toxic effects of lead on the brain. Pups were fed lead, as lead acetate, by esophageal catheter for 14 days beginning at various ages between 14-24 days. The daily lead doses, which produced a hemorrhagic cerebellar encephalopathy in at least 50% of pups, were 400 micrograms Pb/g body weight for animals fed from 14 days of age, 800 micrograms/g for animals fed from 16 days, and 1600 micrograms/g for animals fed from 18 days. In contrast, pups fed even higher lead doses beginning at 20 days showed only a patchy cerebellar edema by light microscopy while pups fed from 24 days had normal cerebellums by light microscopy. The encephalopathic lead doses in the younger pups resulted in the same cerebellar lead concentrations (about 30 micrograms/g protein) as the higher lead doses fed pups beginning at 20 ot 24 days. When corrected for blood lead concentrations, the cerebellar lead concentrations were 20-25% higher in the encephalopathic compared to the older encephalopathy-resistant animals. This difference may be accounted for by cerebellar hemorrhages in the younger animals. Polarographic studies showed inhibition of respiration in cerebellar slices from animals fed lead from 14 days of age but not in animals fed from 20 or 24 days of age. Our results that, during the encephalopathy-sensitive age period, a critical cerebellar concentration of lead is associated with the encephalopathy. Resistance to lead encephalopathy in older animals, with similar cerebellar lead concentrations, may be related to a capacity to sequester lead in new cellular locations away from its site of action on aerobic energy metabolism.

The Pathogenesis of Lead Encephalopathy in the Rat Pup: Effects of Maternal PbCO3 Feedings from Birth

Summary: Rat pups received PbCO3 via maternal feedings from the day of birth. Pb-fed pups showed decreased weight gain, decreased activity, and delayed neurologic development compared to controls in the first 2 weeks of life. The highest frequency of spontaneous deaths and of gross hemorrhagic cerebellar encephalopathy occurred in the second week of Pb feedings. Packed red blood cell volumes decreased progressively in Pb-fed animals, compared to controls, during the 4 weeks of Pb feedings. The increase in Pb content, expressed as a function of homogenate protein, was greater in the cerebellum than the cerebrum after 2 and 4 weeks of Pb feedings. In the first 2 weeks of life, respiration was affected more in mitochondria isolated from the cerebrums than from the cerebellums of Pb-fed animals. Respiratory control ratios with NAD-linked substrates were depressed due to inhibition of state 3 respiration. With succinate as substrate, both state 3 and state 4 respirations were inhibited. In cerebral mitochondria from animals surviving the first 2 weeks of Pb feedings, control ratios and respiratory rates returned toward normal values. Cerebellar mitochondria from Pb-fed animals showed no significant changes in respiration in the first 2 weeks. After 3 and 4 weeks of Pb feedings, control ratios in cerebellar mitochondria were decreased due to a marked increase in state 4 rates with the NAD-linked substrates. Similar but smaller changes occurred with succinate as substrate. Cytochrome oxidase (EC 1.9.3.1) activity showed a progressive increase in both cerebellar and cerebral mitochondria from Pb-fed animals throughout the 4 weeks of lead feedings. Speculation: The age-dependent differences in brain regional mitochondrial sensitivity to Pb effects may be due to regional differences in the time course of maturation. The cerebral mitochondrial effects of early Pb feedings may be important in the changes in learning performance and behavior attributed to early Pb feedings in the neonatal rat and the human infant or fetus.

Paraneoplastic CNS and Renal Syndromes

THE TERM carcinomatous neuromyopathy was introduced by Brain and Henson 1 to describe the neurological syndromes that occur with malignant tumors in the absence of CNS metastases. These paraneoplastic effects of cancer on the CNS are largely manifested clinically as cerebellar degeneration, dementia, myelopathy, encephalopathy, or disorders of the motor unit. To my knowledge, cases of opsoclonus, a rare ocular dyskinesia characterized by rapid and arrhythmic conjugate oscillations of the eyes in all directions, have been reported twice in the past as a remote effect of lung cancer. 2 A patient had development of opsoclonus, dementia, and cerebellar dysfunction as the initial manifestation of an occult oat cell carcinoma of the lung. In addition, this patient suffered from the nephrotic syndrome secondary to an immune-complex glomerulonephritis, presumably of paraneoplastic origin. To my knowledge, this combination of a remote effect of carcinoma on both the CNS and the kidney has not

Cerebellar encephalopathy and neuroblastoma.

A case of cerebellar encephalopathy with neuroblastoma is described, and a brief account is given of current knowledge on the aetiology of the 2 conditions, and possible lines of approach to the patho

The coincidence of neuroblastoma and acute cerebellar encephalopathy

Three patients with neuroblastoma and acute cerebellar encephalopathy are reported. This coincidence of disease occurs more commonly than one would expect on the basis of chance. This observation is supported by the finding of six other cases cited in the literature. The pathogenesis which underlies the relationship is obscure. The authors suggest that all patients with acute cerebellar encephalopathy be surveyed for an inapparent neuroblastoma. The search should include chest and skeletal roentgenograms, intravenous urogram, bone marrow examination for malignant cells, and determination of the urinary excretion of catecholamines and possibly cystathionine.