Magnetic resonance imaging in intractable partial epilepsy: correlative studies

A study was performed evaluating magnetic resonance imaging (MRI) in 35 patients with intractable complex partial seizures in whom computed tomographic (CT) scans showed no focal abnormalities. These results were correlated with positron emission tomography evaluation (PET), the electroencephalographic ictal onset, and findings during pathological examination. Seven patients had structural lesions that were epileptogenic, detected by MRI; the lesions were tuberous sclerosis, astrocytomas, or hamartomas. Three of these 7 patients underwent PET scanning, which was normal in all. Of 18 patients with mesial temporal sclerosis, 10 were shown by PET to have temporal lobe hypometabolism, though all 18 had normal MRI findings. The results indicate that MRI contributes information to that provided by CT and PET, by detecting nonsclerotic epileptogenic lesions of the temporal lobe.     

Fragile X syndrome: associated neurological abnormalities and developmental disabilities

The fragile X syndrome is a frequent cause of developmental disabilities. It is associated primarily with nonprogressive X-linked mental retardation. The neurodevelopmental abnormalities of 25 males and 3 females are described. Mental retardation was mild in 4, moderate in 11, severe in 6, and profound in 2 patients, while 4 patients had only learning disabilities. The presence or absence of a developmental disability could not be determined in the youngest (8 months). Seven patients had had infantile autism and 7 had epilepsy. Generally no major focal neurological abnormalities were observed but most of the patients exhibited minor signs. The severity of developmental disabilities in our patients varied between and within families and between genders. All adult males had macroorchidism. Unusual facial features were present in 13 males but none were seen in the females. Familial occurrences were found in 18 cases (64%); 10 cases (36%) were sporadic. Overall, males were more severely affected than females. Diagnostic tests including computed tomographic scans, electroencephalograms, and evoked potentials did not disclose any specific abnormalities.     

A clinical syndrome of rostral and caudal spinal injury: neurological, neurophysiological and urodynamic evidence for occult sacral lesion.

Patients with spinal cord injury show upper motor neuron dysfunction below the level of the lesion. Some patients with cervical and high thoracic injuries show unexpected lower leg atrophy and ankle jerk abnormalities together with persistence of urinary retention. Clinical, neurophysiological and urodynamic findings in 130 patients with cervical and thoracic injuries showed that 18 patients had additional lumbosacral dysfunction. Three patients had radiological findings demonstrating a second lesion of the lower spine. The remaining 15 patients, however, did not have any obvious bony lesion to account for the lumbosacral dysfunction. Atypical neurological findings, abnormal neurophysiological testing and aberrant detrusor behaviour were the essence of the occult lumbosacral dysfunction in cervical and thoracic spinal cord injury patients. Recognition of the presence of a double lesion was important for care of the neuropathic bladder and pain in addition to understanding the unexpected clinical signs.     

Startle epilepsy: A clinical study

Twelve patients with perinatal anoxic encephalopathy, 1 with encephalitis, and 1 with Down's syndrome had startle epilepsy. Hemiparesis, startle-induced seizures involving the hemiparetic side, focal electroencephalographic abnormalities, and unilateral lesions evident on computed tomographic scan were found in 6 patients, all of whom responded favorably to carbamazepine. The remaining 8 patients had severe intellectual impairment, bilateral motor deficits, generalized startle-induced seizures, diffuse and lasting electroencephalographic abnormalities, and widespread cerebral lesions evident on computed tomographic scan. Of these, 2 patients with Lennox-Gastaut syndrome responded to clonazepam, 4 others responded to valproic acid, and 2 others, with predominantly focal hemispheric lesions, improved on a regimen of carbamazepine.     

Results of computed tomography in "neurologically normal" children after initial onset of seizures

A combined retrospective and prospective study assessed the results of computed tomographic (CT) scans in infants and children without neurologic deficit who presented with initial onset of seizures. Of 101 pediatric patients, 81 had afebrile seizures and 20 had complicated febrile seizures (i.e., focal, multiple, or prolonged). Seven children (7%), 6 with afebrile and 1 with a febrile seizure, had CT abnormalities. Four patients (4%) required further diagnostic workup including angiography and/or surgery. Children with afebrile focal seizures were more likely to have an abnormality than those with afebrile generalized seizures without focal components (13% and 4.9%, respectively). This study demonstrated a lower percentage of overall CT abnormalities, yet a similar percentage of "therapeutically important" abnormalities, in neurologically normal children with new onset of seizures when compared to previous reports of children with chronic seizures. Although an abnormal CT was more likely to be associated with an abnormal electroencephalogram, a normal result did not eliminate the possibility of an abnormal CT.     

Sarcoid peripheral neuropathy.

We studied 10 patients with sarcoidosis and peripheral neuropathy. Six had a subacute or chronic axonal sensorimotor neuropathy without cranial neuropathy, beginning months to years after established systemic sarcoidosis. One patient had severe enough diaphragmatic weakness to require mechanical ventilation. Four patients had atypical neuropathies: acute Guillain-Barré syndrome, mononeuritis multiplex, unilateral lumbosacral plexopathy, and a purely sensory neuropathy, all before systemic sarcoidosis became evident, and all except one had cranial nerve abnormalities. Autopsy in one patient with sensorimotor neuropathy showed only scattered foci of lymphocytes in spinal roots and ganglia with nerve fiber loss.     

Immature pattern of brain activity in Rett syndrome

Seven girls with Rett syndrome, a progressive degenerative encephalopathy affecting girls, were studied with single photon emission computed tomography and compared with an aged-matched control group of nine normal children. Global cerebral blood flow was significantly lower in Rett syndrome (54 vs 69 mL/100 g per minute), and the flows in prefrontal and temporoparietal association regions of the telencephalon were markedly reduced, whereas the primary sensorimotor regions were relatively spared. The flow distribution in Rett syndrome is very similar to the distribution of brain metabolic activity in infants of a few months of age. The abnormal regional cerebral blood flow distribution most likely reflects the widespread functional disturbances in the brain of patients with Rett syndrome, whereas computed tomographic and neuropathologic examination only reveal slight changes when compared with normal children.     

Hemiparesis apparently due to central pontine myelinolysis following hyponatremia

A 63-year-old woman was in an acute confusional state accompanied by rapidly progressive left hemiparesis, dysphagia, and dysarthria two weeks after an episode of diuretic-induced hyponatremia. High-resolution computed tomographic scanning disclosed a circumferential hypodense pontine lesion compatible with the diagnosis of central pontine myelinolysis. Although the patient improved clinically within six weeks, the computed tomographic abnormalities remained unchanged.     

Progressive encephalopathy in children with acquired immune deficiency syndrome

We are reporting the cases of four children with a diagnosis of acquired immune deficiency syndrome (AIDS) who demonstrated a progressive encephalopathy manifested by loss of motor milestones or intellectual abilities, and weakness with pyramidal tract signs. Two patients were ataxic. One child was cortically blind and suffered myoclonic jerks before his death. Two of the patients had isolated seizures at some time during the disease course. Two patients developed secondary microcephaly and all four patients showed cortical atrophy on computed tomographic scanning. Three of the patients died. Postmortem neuropathological findings included gross cortical atrophy, microglial nodules, and intranuclear inclusions, as are described in the subacute encephalitis reported in adult AIDS patients. We propose that the possible pathogenetic mechanisms of this encephalopathy include opportunistic or persistent viral infection of the brain.     

PET scan investigations of Huntington's disease: cerebral metabolic correlates of neurological features and functional decline

Fifteen drug-free patients with early to midstage Huntington's disease were evaluated with quantitative neurological examinations, scales for functional capacity, computed tomographic (CT) scans, and positron emission tomographic (PET) scans of 18F-2-fluoro-2-deoxyglucose (18F-FDG) uptake. All patients had abnormal indices of caudate metabolism on PET scanning, whereas in patients with early disease indices of putamen metabolism and CT measures of caudate atrophy were normal. Indices of caudate metabolism correlated highly with the patients' overall functional capacity (r = 0.906; p less than 0.001) and bradykinesia/rigidity (r = -0.692; p less than 0.01). Indices of putamen metabolism correlated highly with motor functions: chorea (r = -0.841; p less than 0.01), oculomotor abnormalities (r = -0.849; p less than 0.01), and fine motor coordination (r = -0.866; p less than 0.01). Indices of thalamic metabolism correlated positively with dystonia (r = 0.559; p less than 0.05). The data suggest that PET scanning with 18F-FDG is a sensitive measure of brain dysfunction in Huntington's disease and that basal ganglia metabolism is highly correlated with the overall functional capacity of individual patients and with the degree of their motor abnormalities.     

Asymptomatic cerebral infarction in patients with chronic atrial fibrillation

A retrospective analysis of 54 patients with atrial fibrillation presenting with symptoms of cerebral ischemia between 1980 and 1985 was performed. Seven patients (13%) had computed tomographic evidence of previous, clinically silent cerebral infarction. In a control group of 168 persons (studied prospectively) in sinus rhythm presenting with symptoms of cerebral ischemia, seven (4%) had computed tomographic evidence of previous, clinically silent cerebral infarction (p less than 0.05). In those patients with atrial fibrillation all infarcts were peripheral and consistent with embolism, while in three of the seven patients in sinus rhythm the asymptomatic infarcts were lacunes.     

Reduced cerebral blood flow in early stages of human immunodeficiency virus infection

In order to determine if brain perfusion abnormalities, which are known in patients with acquiredimmunodeficiency syndrome dementia, occur in early stages of human immunodeficiency virus infection, technetium 99m hexamethyl-propyleneamine oxime-single-photon emission computed tomography studies were performed in 20 patients infected with human immunodeficiency virus who belonged to Walter Reed stages I through IV. None of these patients demonstrated signs of dementia or severe neurological dysfunction. Pathological patterns of hexamethyl-propyleneamine oxime uptake were seen in 14 patients, seven of whom had normal results during neurological examination. Only four patients had signs of cerebral atrophy on cranial computed tomographic scan. These data suggest that subtle changes in cerebral perfusion seem to arise early in the course of human immunodeficiency virus infection and may indicate human immunodeficiency virus encephalopathy before neurological symptoms or noticeable structural damage occurs.     

Pediatric cerebrovascular disease. Alterations of regional cerebral blood flow detected by TC 99m-HMPAO SPECT

Regional cerebral blood flow (rCBF) alterations, as determined by single photon emission computed tomography (SPECT) using technetium Tc 99m hexamethyl propylenamine oxime (Tc 99m-HM-PAO), were studied in 15 infants and children presenting with cerebrovascular disorders between the ages of 2 weeks and 16 years. The rCBF patterns were correlated with clinical presentation, electroencephalographic patterns, radiologic studies, including computed tomography and magnetic resonance imaging of the head, and cerebral angiography. All patients presented with motor weakness that was accompanied in some with dysphasia, defects in visual fields, obtundation, seizures, and high temperature. Perturbations of rCBF with Tc 99m-HMPAO SPECT brain scanning were detected in all patients investigated, with no adverse effects related to the radiotracer. All patients had a focal area of decreased rCBF, with adjacent hyperemia in 3 patients. In 7 patients, there was an rCBF decrease in a vascular distribution, mainly that of the middle cerebral artery, that correlated with the clinical findings and a focal electroencephalogram, as well as computed tomography and magnetic resonance imaging of the head. Impairment of rCBF was more extensive in 3 children, while early abnormal SPECT findings preceded abnormal computed tomographic findings in another 2 children. In 2 patients, Tc 99m-HMPAO SPECT was the only positive radiologic test to correlate with focal clinical and electroencephalographic abnormalities, in view of repeated normal computed tomographic scans. We conclude that Tc 99m-HMPAO SPECT brain scanning is a sensitive, complementary diagnostic measure in the early detection, localization, and estimation of rCBF alterations in pediatric cerebrovascular disease.     

Unusual manifestations of herpes zoster. A clinical and electrophysiological study.

The literature on complicated herpes zoster is summarized in this paper. The case histories of 18 patients with herpes zoster are presented. Two patients had encephalitis, 2 had myelitis and the other 14 patients had various types of lower motor neurone disturbance. Both patients with encephalitis--one of who developed choreo-athetosis during the illness--recovered fully. Only 1 of the 2 patients with myelitis recovered fully; the other remains severely paraparetic and the reason for her incomplete recovery may be related to the presence of generalized arteriolar disease associated with seronegative rheumatoid disease. One patient developed a Guillain-Barre syndrome 3 weeks after the onset of herpes zoster. Recovery in the 15 patients with lower motor neurone involvement has been slow butcomplete--or almost complete--in all but 1, a patient with persistent facial weakness as part of the Ramsay Hunt syndrome and who also had weakness of one upper limb. Seven other patients had lower limb weakness. In 2 patients the weakness was confined to abdominal myotomes and 2 other patients had urinary retention. Electromyographic abnormalities were found in the muscles which were weak and frequently also in muscles which appeared strong. It is emphasized that neurological disturbances other than sensory abnormalities may be found in patients with herpes zoster. Motor complications of various types are not uncommon.     

The value of visual evoked potential as a screening test in neurofibromatosis

Pattern reversal visual evoked potential (VEP) test was performed in 30 asymptomatic patients with neurofibromatosis (NF). All patients had normal visual acuity, visual fields, and ophthalmoscopic examination results. Pattern reversal VEP was abnormal in eight patients (26%). Seven of these patients had computed tomographic scans with reformated orbital views. Orbital computed tomographic scans were abnormal in six patients and in each case showed enlargement of the optic nerve on the side of VEP abnormality. Our data indicate that pattern reversal VEP is a valuable screening test in asymptomatic patients with NF. Because of the high incidence of VEP abnormality in such patients, VEP abnormality must be interpreted cautiously when a patient with NF is suspected of having other diseases or disorders that potentially affect the visual pathways.     

Spinal segmental somatosensory evoked potentials in lumbosacral radiculopathies

We studied 21 patients with lumbosacral radiculopathy with segmental somatosensory evoked potentials (SEPs) recorded over both spine and scalp following saphenous, superficial peroneal, and sural nerve stimulation. Spinal SEPs were abnormal in 10 patients. In 3 patients, SEPs detected abnormalities not seen on EMG examination. With 1 exception, all anatomic levels of SEP abnormalities matched that of radiographic, EMG, or clinical abnormalities. SEPs were abnormal in 41% of nerve roots shown to be involved by other techniques. SEPs added to the clinical evaluation in 4 patients, but were less accurate than a combination of EMG and radiography in indicating the extent of nerve root involvement. We conclude that spinal SEPs following segmental sensory stimulation are useful in the evaluation of lumbosacral radiculopathies and complement information provided by the EMG. In contrast, scalp-recorded segmental SEPs rarely provide additional useful clinical information.     

Congenital fibre type disproportion with unusual clinico-pathologic manifestations.

Two cases with congenital fibre type disproportion are presented. The cases are unusual in that there were significant dysmorphic features in case 1, and both cases showed electromyographic abnormalities suggestive of denervation. A third case, the father of the second patient, showed clinical features of congenital fibre type disproportion in early life but later developed the rigid spine syndrome. The spinal cord of case 3 showed atrophy and degeneration of medial neuronal group in the lumbosacral segments. The clinical and pathological features in these cases further extend the view that congenital fibre type disproportion may be seen in a variety of patients.     

Nontumoral occipitotemporal epilepsy: localizing findings and surgical outcome

We describe a syndrome of medically intractable occipitotemporal epilepsy of nontumoral developmental origin and its treatment by surgery. From our epilepsy surgery database of 1988 to 1996, we selected all patients without neoplasm who had at least two characteristics localizing to the occipital lobe (clinical symptoms, interictal focus, ictal onset, or a lesion on magnetic resonance imaging scanning) and one to the temporal lobe (interictal spikes or seizure onset). We discuss seizure characteristics, electroencephalographic (EEG), magnetic resonance imaging, positron emission tomographic, and single-photon emission computed tomographic findings, pathological findings, surgical approach, outcome from resective surgery, and implications for pathophysiology. Sixty-nine percent of our 16 patients with occipitotemporal syndrome had neuronal migration disorder, suggesting a developmental etiology of this entity. Initial signs or symptoms suggested occipital lobe seizure onset in 13 of 16 patients. On scalp EEG, interictal spikes were localized to the temporal lobe in 9 and to the occipital lobe in 1; seizure onset was poorly localized. Intracranial EEG localized seizure onset to the area of temporo-occipital junction in 77% of patients. Positron emission tomography and single-photon emission computed tomography showed occipital and temporal or widespread deficits, and neuropsychological performance was diffusely abnormal. Surgical results were best with occipital and temporal resections, but sometimes satisfactory after occipital resection even with temporal (ipsilateral) EEG findings. Temporal resection with hippocampectomy uniformly failed to control seizures. An often refractory, probably developmental epileptic syndrome with regional occipitotemporal distribution can be diagnosed by a specific constellation of findings, which has implications for treatment and pathophysiology.     

Slowly progressive aphasia without generalized dementia: studies with positron emission tomography

Slowly progressive aphasia without generalized dementia is a degenerative syndrome selectively affecting dominant hemisphere language areas. We report changes in regional glucose metabolism measured by positron emission tomography in two patients with this condition. Striking abnormalities of glucose utilization in the left cerebral cortex were demonstrated in both patients. The findings of other neurodiagnostic studies were relatively unremarkable. The first patient had a 3-year history of progressive anomia and impaired auditory verbal recall. An electroencephalogram was normal, and computed tomography showed mild left perisylvian atrophy. Positron emission tomography revealed profound hypometabolism in the left temporal regions. The second patient also had a 3-year history of progressive anomia. Electroencephalography, computed tomography, and magnetic resonance imaging scans were normal. Positron emission tomography showed a major reduction in left parietal glucose utilization, with a lesser decrement in left temporal metabolism. Neither patient demonstrated significant contralateral or global abnormalities such as those reported in positron emission tomographic studies of Alzheimer's disease with or without focal clinical features. These observations support the concept of adult-onset progressive aphasia without dementia as a clinical syndrome distinct from Alzheimer's disease.     

The Lennox-Gastaut syndrome: metabolic subtypes determined by 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography

We employed positron emission tomography (PET) with 2-deoxy-2[18F]fluoro-D-glucose (FDG) to study local cerebral glucose utilization in 15 children who had Lennox-Gastaut syndrome. Our results show that LGS can be classified into four predominant subtypes, each with a distinct metabolic pattern: unilateral focal hypometabolism, unilateral diffuse hypometabolism, bilateral diffuse hypometabolism, and normal. Functional disturbances seen on FDG-PET did not always correlate with abnormalities revealed by x-ray computed tomographic scan. This classification of Lennox-Gastaut syndrome into four major metabolic subtypes not only provides a new perspective toward understanding cerebral function in this complex syndrome, but may also prove useful in the clinical management of these patients.