Neural correlates of regional EEG power change.

To clarify the physiological significance of task-related change of the regional electroencephalogram (EEG) rhythm, we quantitatively evaluated the correlation between regional cerebral blood flow (rCBF) and EEG power. Eight subjects underwent H2 15O positron emission tomography scans simultaneously with EEG recording during the following tasks: rest condition with eyes closed and open, self-paced movements of the right and left thumb and right ankle. EEG signals were recorded from the occipital and bilateral sensorimotor areas. Cortical activation associated with EEG rhythm generation was studied by the correlation between rCBF and EEG power. There were significant negative correlations between the sensorimotor EEG rhythm at 10-20 Hz on each side and the ipsilateral sensorimotor rCBF and between the occipital EEG rhythm at 10-20 Hz and the occipital rCBF. The occipital EEG rhythm showed a positive correlation with the bilateral medial prefrontal rCBF, while the right sensorimotor EEG rhythm showed a positive correlation with the left prefrontal rCBF. In conclusion, decrease in the regional EEG rhythm at 10-20 Hz might represent the neuronal activation of the cortex underlying the electrodes, at least for the visual and sensorimotor areas. The neural network including the prefrontal cortex could play an important role to generate the EEG rhythm.

Open-label dose-escalation study of oral 1-octanol in patients with essential tremor.

Twenty-one single oral doses of 1-octanol were given to patients with essential tremor (ET) in an open-label dose-escalation study. The drug was well tolerated up to 64 mg/kg. The main side effect was an unusual taste. No overt intoxication was seen. There was evidence for efficacy, with a significant reduction in tremor amplitude as measured by accelerometry and handwriting that was maximal at 2 hours. Higher doses may produce more sustained benefit.

Pilot trial of 1-octanol in essential tremor.

1-Octanol (an 8-C alcohol currently used as a food-flavoring agent) is known to inhibit tremor in essential tremor (ET) animal models at a much lower dose than ethyl alcohol. The authors conducted a randomized, placebo-controlled pilot trial of a single oral dose of 1 mg/kg of 1-octanol in 12 patients with ET. No significant side effects or signs of intoxication were observed. 1-Octanol significantly decreased tremor amplitude for up to 90 minutes. The results suggest 1-octanol as a well-tolerated and safe potential treatment for ET. Further trials are warranted.

Anti-ganglioside antibodies in idiopathic and hereditary cerebellar degeneration.

Cerebellar degeneration has been associated with gluten sensitivity and celiac disease. Patients with celiac disease may have neuropathy and antibodies to gangliosides. The authors investigated the presence of antiganglioside antibodies in 22 patients with hereditary and nonhereditary ataxia and found 64% reactive in a novel agglutination test.

Multiple tactile maps in the human cerebellum.

Functional imaging studies of the cerebellum have mostly investigated motor performance or have been limited to the anterior lobe and therefore the somatosensory representations in the human cerebellum have not been fully demonstrated. We used fMRI of the entire cerebellum during tactile stimulation of the hand and foot in six normal subjects. Our results demonstrate that the tactile projections to the cerebellum in humans are represented in both the anterior and posterior lobes. in agreement with previous functional imaging studies, our results show a large-scale, between-limb somatotopy comparable to that shown in early animal studies.

Gluten sensitivity in sporadic and hereditary cerebellar ataxia.

Gluten sensitivity, with or without classical celiac disease symptoms and intestinal pathology, has been suggested as a potentially treatable cause of sporadic cerebellar ataxia. Here, we investigated the prevalence of abnormally high serum immunoglobulin A (IgA) and IgG anti-gliadin antibody titers and typical human lymphocyte antigen (HLA) genotypes in 50 patients presenting with cerebellar ataxia who were tested for molecularly characterized hereditary ataxias. A high prevalence of gluten sensitivity was found in patients with sporadic (7/26; 27%) and autosomal dominant (9/24; 37%) ataxias, including patients with known ataxia genotypes indicating a hitherto unrecognized association between hereditary ataxias and gluten sensitivity. Further studies are needed to determine whether gluten sensitivity contributes to cerebellar degeneration in patients with hereditary cerebellar ataxia. Patients with hereditary ataxia (including asymptomatic patients with known ataxia genotype) should be considered for screening for gluten sensitivity and gluten-free diet trials.

Neural correlates of auditory-visual stimulus onset asynchrony detection.

Intersensory temporal synchrony is an ubiquitous sensory attribute that has proven to be critical for binding multisensory inputs, sometimes erroneously leading to dramatic perceptual illusions. However, little is known about how the brain detects temporal synchrony between multimodal sensory inputs. We used positron emission tomography to demonstrate that detecting auditory-visual stimulus onset asynchrony activates a large-scale neural network of insular, posterior parietal, prefrontal, and cerebellar areas with the highest and task-specific activity localized to the right insula. Interregional covariance analysis further showed significant task-related functional interactions between the insula, the posterior thalamus, and superior colliculus. Based on these results and the available electrophysiological and anatomical connectivity data in animals, we propose that the insula, via its known short-latency connections with the tectal system, mediates temporally defined auditory-visual interaction at an early stage of cortical processing permitting phenomena such as the ventriloquist and the McGurk illusions.

Enhanced excitability of the human visual cortex induced by short-term light deprivation.

Long-term deprivation of visual input for several days or weeks leads to marked changes in the excitability and function of the occipital cortex. The time course of these changes is poorly understood. In this study, we addressed the question whether a short period of light deprivation (minutes to a few hours) can elicit such changes in humans. Noninvasive transcranial magnetic stimulation (TMS) of the human occipital cortex can evoke the perception of flashes or spots of light (phosphenes). To assess changes in visual cortex excitability following light deprivation, we measured the minimum intensity of stimulation required to elicit phosphenes (phosphene threshold) and the number of phosphenes elicited by different TMS stimulus intensities (stimulus-response curves). A reduced phosphene threshold was detected 45 min after the onset of light deprivation and persisted for the entire deprivation period (180 min). Following re-exposure to light, phosphene thresholds returned to predeprivation values over 120 min. Stimulus-response curves were significantly enhanced in association with this intervention. In a second experiment, we studied the effects of light deprivation on functional magnetic resonance imaging (fMRI) signals elicited by photic stimulation. fMRI results showed increased visual cortex activation after 60 min of light deprivation that persisted following 30 min of re-exposure to light. Our results demonstrated a substantial increase in visual cortex excitability. These changes may underlie behavioral gains reported in humans and animals associated with light deprivation.

Modality-specific frontal and parietal areas for auditory and visual spatial localization in humans.

Although the importance of the posterior parietal and prefrontal regions in spatial localization of visual stimuli is well established, their role in auditory space perception is less clear. Using positron emission tomography (PET) during auditory and visual spatial localization in the same subjects, modality-specific areas were identified in the superior parietal lobule, middle temporal and lateral prefrontal cortices. These findings suggest that, similar to the visual system, the hierarchical organization of the auditory system extends beyond the temporal lobe to include areas in the posterior parietal and prefrontal regions specialized in auditory spatial processing. Our results may explain the dissociation of visual and auditory spatial localization deficits following lesions involving these regions.

A PET study of human auditory spatial processing.

To learn more about human auditory spatial processing, we used positron emission tomography (PET) to measure regional cerebral blood flow in human volunteers engaged in sound localization tasks. Spectral and binaural cues of localized sound were reproduced by a sound system and delivered via headphones. During localization tasks, subjects activated inferior parietal lobules (IPL) bilaterally. In a second experiment, matched in design to the first, subjects made non-spatial auditory discriminations based on frequency, activating the IPL bilaterally with left hemispheric predominance. A between-study comparison revealed that the right IPL was significantly more activated during the sound localization task compared with the feature discrimination task, suggesting a preferential role for the right IPL in auditory spatial processing.

Reversible MRI lesions due to pegaspargase treatment of non-Hodgkin's lymphoma.

L-Asparaginase is the major induction-phase agent for treatment of acute lymphoblastic leukemia (ALL) and an important adjuvant in treatment of non-Hodgkin's lymphoma (NHL). However, L-asparaginase-induced disturbances of clotting homeostasis may result in thrombosis or hemorrhage. Thrombotic occlusion of small cerebral veins has been reported in patients with ALL treated with this agent, but have not been described in NHL patients or those treated with the long-acting synthetic congener, pegaspargase. We report a 16-year-old boy with NHL who developed a focal motor seizure 15 min after receiving intravenous pegaspargase. MRI of the brain demonstrated multiple cortical and subcortical lesions that most likely represented focal brain edema due to thrombotic venous occlusion, which improved remarkably within 3 days and completely resolved within 3 weeks without specific intervention or permanent clinical consequences. This process must be considered when such changes are detected in NHL patients.

Epidemic heat stroke in a midwest community: risk factors, neurological complications and sequelae.

We studied the admission rate, risk factors, neurological complications and sequelae of heat stroke (HS) during the 1995 heat wave in Madison, Wisconsin. HS was epidemic in 1995 (2.3 cases/1000 admissions), compared to the ten-fold lower endemic rate in 1994 (0.2/ 1000). There were 11 cases of HS, 9 males and 2 females. Contributing factors were athletic events (2), working outdoors (3) and indoor activity with malfunctioning air-conditioning (6). Medical conditions contributing to poor temperature regulation included schizophrenia with neuroleptic treatment (2), amyotrophic lateral sclerosis receiving nortriptiline (1), multiple sclerosis (1), attention deficit disorder (1), cystic fibrosis (1) and alcoholism (1). Acute neurological complications occurred in all patients on presentation including coma (8/11.73%), stupor (2/ 11.18%) and seizures (1/11.9%). Two patients (1856) had persistent neurological sequelae in the form of a pan-cerebellar syndrome while the remaining 9 recovered fully. Importantly, avoidable factors contributed to all of the patients with underlying diseases. These patients are particularly at risk and should take adequate precautions during summer months.

Sialorrhea in amyotrophic lateral sclerosis: a hypothesis of a new treatment--botulinum toxin A injections of the parotid glands.

The inhibitory action of botulinum toxin is not confined to the neuromuscular junction. The toxin has long been known to block all the autonomic cholinergic fibers, including the major secretomotor parasympathetic fibers to salivary glands. The parotids are the largest of the salivary glands and their selective chemodenervation with botulinum toxin A is likely to result in substantial reduction of saliva production. Injection of the parotid glands with botulinum toxin is proposed as an new treatment for sialorrhea in patients with amyotrophic lateral sclerosis and other neurological diseases.

Botulinum toxin--a possible new treatment for axillary hyperhidrosis.

The inhibitory action of botulinum toxin is not limited to the neuromuscular junction. The toxin also blocks the autonomic cholinergic fibres, including the sympathetic fibres to sweat glands. We have previously demonstrated that the toxin produces localized anhidrosis. To determine the dosage, pattern and duration of the anhidrotic effect of botulinum toxin and to test the efficacy of axillary injections, we further studied seven healthy volunteers. Two individuals had subcutaneous injections of botulinum toxin (20 mouse units, Dysport-Porton Products) in the dorsum of the hand. Five healthy volunteers had 15-50U of botulinum toxin A (Botox) injected in one axilla. A circular area of complete anhidrosis on the dorsum of the hand was evident on day 2 and persisted for 11 months. By day 3, two of the axillae (injected with 50 U each) were totally dry and in one (injected with 30 U) the sweating was substantially reduced. The effect persisted for 6-8 months before wearing off. No effect was appreciated in two axillae (injected with 15 and 20 U). No significant side-effects were encountered. Subcutaneous injections of botulinum toxin causes chemodenervation of the sweat glands. In normal individuals axillary sweating can be abolished by 50 U of botulinum toxin A (Botox). The results offer a possible novel treatment for severe cases of axillary hyperhidrosis.

Sarcoidosis of the spinal cord with extensive vertebral involvement: a case report.

We report on a patient with systemic sarcoidosis who was presented with myelopathy and backache. Plain spinal films were normal, CT scan showed sclerotic lesions within the vertebrae. MRI showed more extensive involvement of the spine with multiple vertebral lesions which were hypointense on both T1W1 and T2W1 and did not enhance with gadolinium. MRI also showed high signal lesions within the cervical and lumbar spinal cord on T2-weighted images (T2W1) which were isointense on T1-weighted images (T1W1) and did not enhance. Vertebral biopsy results were consistent with the diagnosis of sarcoidosis. MRI is very sensitive in detecting sarcoidosis of bone but non-specific and other types of sclerotic or lytic bone lesions (notably metastases) need to be excluded.