Botulism may involve the autonomic nervous system.

We assessed the autonomic function of 6 botulism patients with heart rate variations, sympathetic skin responses, and plasma norepinephrine.

Two weeks after onset, all the patients had absent sympathetic skin response in the palm and sole. Compared with controls, the heart rate variation of botulism patients was significantly decreased at rest (3.1 ± 1.2% vs. 20.9 ± 2.0%, p = 0.0018) and during deep breathing (4.3 ± 2.3% vs. 29.7 ± 2.6%, p = 0.0018). The botulism patients had significantly lower plasma norepinephrine levels (supine 29.2 ± 10.1 pg/ml vs. 257.5 ± 65.8 pg/ml, p = 0.0018; standing 40.3 ± 13.1 pg/ml vs. 498.5 ± 85.6 pg/ml, p = 0.0018). The heart rate variation and sympathetic skin response was greatly improved 6 months after onset.

Heart rate variation, absence of sympathetic skin response, and low plasma norepinephrine are all manifestations of autonomic dysfunction in botulism patients.

The prognostic significance of epileptiform activity (EA) recorded intraoperatively at electrocorticography (ECOG) in patients with lesion-related frontal lobe epilepsy (FLE) is unknown.

The results of ECOG performed in 22 patients with intractable FLE and a circumscribed frontal lobe structural lesion were compared with postoperative seizure control. Three patients underwent re-operation for a total of 25 cases, 23/25 with post-resection ECOG. Lesions were neoplasms (12), hamartomas (6) and arteriovenous malformations (4).

Outcomes were 15/25 Class I, 5/25 Class III and 5/25 Class IV (Engel classification). Class I outcome was associated with pre-excision EA recorded from ≤ 2 gyri (p < 0.05) and absence of EA, or EA limited to the resection border, at post-excision ECOG (p < 0.01). Complete lesion excision was highly correlated with Class I outcome (p < 0.001). The most significant correlations were seen when ECOG and lesionectomy variables were considered together: all 12 cases with complete lesionectomy and absent post-excision EA distant to the resection border had Class I outcome (p < 0.00015) and all 13 cases with complete lesionectomy and pre-excision EA recorded from ≤ 2 gyri had Class I outcome (p < 0.00005).

Postoperative seizure control in lesion-related FLE is assured in the setting of complete lesion resection with pre-excision EA recorded from ≤ 2 gyri and no post-excision EA distant to the resection border; complete lesion excision is of paramount importance.

One of the difficulties with lumboperitoneal (LP) shunts has been non-invasively ascertaining shunt function. It has been previously reported that in the presence of a functioning LP shunt the perimesencephalic cisterns become obliterated – the “absent cistern sign”. In order to more rigorously test this association we performed a retrospective analysis of LP shunt patients at the Hospital for Sick Children, Toronto.

The CT scans of all patients undergoing LP shunting over a 17 year period were reviewed. The “absent cistern sign” and ventricular size were compared against the results of either an isotope shunt study or surgical findings performed within 2 days of the CT.

There were 38 CT scans (27 patients) performed within 2 days of an isotope shunt study and 15 CT scans (14 patients) performed within 2 days of a surgical intervention. These results give the absent cistern sign a sensitivity of 75% and a specificity of 57% when compared to the shunt isotope findings and a sensitivity of 100% and a specificity of 50% when compared to the surgical findings. Over 30% of the CT scans showed ventriculomegaly in the presence of a functioning shunt and, conversely, nearly 45% of the CT scans had normal or small lateral ventricles in the presence of a malfunctioning shunt.

The “absent cistern sign” appears to reliably rule out a completely blocked shunt, but is less reliable in detecting a normal or partially obstructed shunt. Ventricular size correlates poorly with LP shunt function.

Electromyography (EMG) is a useful test, but unfortunately also painful. We frequently encounter patients who worry about its painful nature, but tolerate it very well. Objectives: We evaluated anxiety levels of patients referred for EMG to explore the possible correlating and contributing factors to high anxiety.

A structured questionnaire, including the State-Trait Anxiety Inventory was completed by patients immediately before EMG testing. Emergency, hospitalized, and seriously ill patients were excluded.

Seventy-nine cases with ages ranging from 19-72 years (mean 43) were included. Thirty-five (44%) patients had a high pre-test anxiety level. The likelihood of high anxiety was increased if the patient was worried about the test (p<0.001) or about other issues unrelated to the test or underlying diagnosis (p<0.001), or was taking an anti-psychotic or anxiolytic drug (p=0.008). The degree or source of knowledge regarding the test procedure, did not affect the pre-test anxiety level.

The information about EMG testing received by patients in this group did not affect pre-test anxiety levels. The patient's expectations regarding the test did influence anxiety levels and this may reflect generalized anxiety regarding testing procedures or misinformation regarding the nature of the test, as patients in general reported a better than anticipated experience following the test.

The majority of patients with diffuse Lewy body disease have cognitive or psychiatric manifestations as part of their initial presentation. A sizable minority present with parkinsonian features alone. Autonomic features may also occur, typically after the development of cognitive changes. We aim to demonstrate that diffuse Lewy body disease may rarely also present with parkinsonism accompanied by marked autonomic dysfunction in the absence of significant cognitive or psychiatric abnormalities.

Case report based on a retrospective chart review and neuropathological examination.

We report on a patient in whom a clinical diagnosis of multiple system atrophy was made based on a presentation of parkinsonism with prominent and early autonomic involvement. The former included postural tremor, rigidity and bradykinesia, while the latter consisted of repeated falls due to orthostasis and the subsequent development of urinary incontinence midway through the course of her illness. She was poorly tolerant of dopaminergic therapy due to accentuated orthostasis. Benefit from levodopa was limited and only evident when attempted withdrawal resulted in increased rigidity. There was no history of spontaneous or drug-induced hallucinations, delusions or fluctuating cognition, and in contrast to the prominence and progression of her parkinsonian and autonomic features over the first several years, cognitive impairment did not occur until the final stages of her illness, seven years after the onset of initial symptoms. Neuropathological examination revealed numerous Lewy bodies in both neocortical as well as subcortical structures consistent with a diagnosis of diffuse Lewy body disease. There was marked neuronal loss in the substantia nigra as well as the autonomic nuclei of the brainstem and spinal cord.

In addition to cognitive, psychiatric, and parkinsonian presentations, diffuse Lewy body disease may present with parkinsonism and prominent autonomic dysfunction, fulfilling proposed criteria for the striatonigral form of MSA.

Tracer constants (Ki) for blood-to-brain diffusion of sucrose were measured in the rat to profile the time course of blood-brain barrier injury after temporary focal ischemia, and to determine the influence of post-ischemic hypothermia.

Spontaneously hypertensive rats were subjected to transient (2 hours) clip occlusion of the right middle cerebral artery. Reperfusion times ranged from 1.5 min to 46 hours, and i.v. 3H-sucrose was circulated for 30 min prior to each time point (1h, 4h, 22h, and 46h; n=5-7 per time point). Ki was calculated from the ratio of parenchymal tracer uptake and the time-integrated plasma concentration. Additional groups of rats (n=7-8) were maintained either normothermic (37.5oC) or hypothermic (32.5oC or 28.5oC) for the first 6 hours of reperfusion, and Ki was measured at 46 hours.

Rats injected after 1.5 - 2 min exhibited a 10-fold increase in Ki for cortical regions supplied by the right middle cerebral artery (p<0.01). This barrier opening had closed within 1 to 4 hours post-reperfusion. By 22 hours, the blood-brain barrier had re-opened, with further opening 22 and 46 hours (p<0.01), resulting in edema. Whole body hypothermia (28oC-29oC) during the first six hours of reperfusion prevented opening, reducing Ki by over 50% (p<0.05).

Transient middle cerebral artery occlusion evokes a marked biphasic opening of the cortical blood-brain barrier, the second phase of which causes vasogenic edema. Hypothermic treatment reduced infarct volume and the late opening of the blood-brain barrier. This opening of the blood-brain barrier may enhance delivery of low permeability neuroprotective agents.

Brainstem auditory evoked potentials (BAEP) are useful indicators of auditory function during posterior fossa surgery. Several potential mechanisms of injury may affect the cochlear nerve, and complete loss of BAEP is often associated with postoperative hearing loss. We report two cases of intraoperative auditory loss related to vascular compression upon the cochlear nerve.

Intra-operative BAEP were monitored in a consecutive series of over 300 microvascu-lar decompressions (MVD) performed in a recent twelve-month period. In two patients undergoing treatment for trigeminal neuralgia, BAEP waveforms suddenly disappeared completely during closure of the dura.

The cerebello-pontine angle was immediately re-explored and there was no evidence of hemorrhage or cerebellar swelling. The cochlear nerve and brainstem were inspected, and prominent vascular compression was identified in both patients. A cochlear nerve MVD resulted in immediate restoration of BAEP, and both patients recovered without hearing loss.

These cases illustrate that vascular compression upon the cochlear nerve may disrupt function, and is reversible with MVD. Awareness of this event and recognition of BAEP changes alert the neurosurgeon to a potential reversible cause of hearing loss during posterior fossa surgery.

To summarize the evidence for neurologic uses of immunoglobulin, intravenous (IGIV) in light of present-day clinical usage. This summary guided the development of practice recommendations for the effective and efficient use of IGIV in Neurology.

MEDLINE was searched to identify pertinent English-language review articles and original reports (n = 231) on the use of IGIV in neurology (excluding editorials, letters, and comments) published before March 1998. Evidence on alternative therapies was only included as compared to IGIV. The relevant original reports and review articles and older classic studies (n = 92) were synthesized into an information foundation. Extracted data included laboratory and clinical findings, objective measures, and clinical impressions. Clinical recommendations were based on evidence quality, graded by study design, clinical experiences of IGIV in Neurology Advisory Board members, and the conditions of IGIV use in therapy.

In neurology, many disorders are poorly understood, and the mechanisms behind beneficial regimens even less so. As a result, it is fairly common for best-practice decisions to rest on weaker evidence. The usefulness of IGIV in neurology can be described by a “combined score” based on evidence quality and strength of impact. Combined scores ranged from A+ (strongly recommended) to C (recommended as a last resort). The following clinical recommendations are made: IGIV is: strongly recommended for the treatment of Guillain-Barré syndrome (A+); favorably recommended for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy, dermatomyositis, and multifocal motor neuropathy (A); recommended as a second resort for the treatment of multiple scerosis and myasthenia gravis (B); and recommended as a last resort for the treatment of polymyositis, inclusion-body myositis, intractable epilepsies, and stiff-man syndrome (C).

To describe the clinical and angiographic results of endovascular occlusion of basilar bifurcation aneurysms with electrolytically detachable coils, and to identify factors which should be considered in deciding upon surgical or endovascular treatment.

We report our experience with 40 patients in whom occlusion of basilar bifurcation aneurysms with electrolytically detachable coils was attempted. All patients underwent superselective angiography and attempted embolization with Guglielmi detachable coils (GDCs). Angiographic and clinical results were prospectively recorded. Twenty-eight aneurysms presented with subarachnoid hemorrhage (SAH), 2 were symptomatic and 10 were incidental.

Coils were not placed in 10 patients (25%) because of unfavorable anatomy. Complete aneurysm occlusion was achieved at the time of the initial procedure in 13 (32.5%), small neck remnants were present in 13 (32.5%), and in 4 (10.0%) there was obvious residual contrast filling of the aneurysm body. Of 23 patients successfully coiled after SAH, 20 were Grade 1 to 3 and 3 were grade 4 or 5 at the time of treatment. Eighteen (78%) made a good recovery. Procedural mortality was 2.5% and permanent morbidity was 7.5%. There were no permanent complications in patients with unruptured aneurysms. Complete aneurysm occlusion was possible in 10 (56%) of 18 aneurysms with small necks and 3 (14%) of 22 with large necks. Follow-up angiography in 25 of 28 surviving patients (mean, 12 months) demonstrated stability of all completely occluded aneurysms. Incompletely coiled aneurysms had variable results on follow-up angiograms: 15.4% improved, 69.2% worsened, and 15.4% were stable. No aneurysm bled after treatment during clinical follow-up averaging 22 months.

Endovascular treatment of basilar bifurcation aneurysms appears to prevent early aneurysm rebleeding with acceptable rates of morbidity and mortality, but long-term follow-up is required.

Cerebral venous thrombosis is a clinical entity which is readily diagnosed with the advent of modern imaging techniques. Anticoagulation is now a standard therapy, but more recent treatment strategies have included endovascular thrombolysis. While the endpoint of this intervention both clinically and radiographically has not been defined, noninvasive monitoring techniques may add further objective measures of treatment response.

We present a patient with a four day history of worsening headache and papilledema on exam. Superior sagittal, straight, and bilateral transverse sinus thromboses were identified on computed tomography and angiography.

Emergent endovascular thrombolysis by a transvenous approach re-established venous patency and resulted in immediate resolution of the patient's symptoms. Cerebral oximetry by near-infrared spectroscopy was utilized during the procedure, and changes in chromophore concentrations correlated directly with angiographic and clinical resolution of the thrombosis.

Near-infrared spectroscopy can provide continuous feedback during thrombolytic therapy in cerebral venous thrombosis and may help define endpoints of such intervention.

3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) is a key rate-limiting enzyme in the mevalonate pathway, which generates precursors for cholesterol biosynthesis and the production of non-steroidal mevalonate derivatives that are involved in a number of growth-regulatory processes. We have reported that lovastatin, a competitive inhibitor of HMG-CoA reductase, not only inhibits medulloblastoma proliferation in vitro, but also induces near-complete cell death via apoptosis. The present study explores some of the pathways which may be involved in lovastatin-induced apoptosis.

Medulloblastoma cell lines were exposed in vitro to lovastatin with or without mevalonate, and document the effects using morphology, flow cytometry, DNA electrophoresis and Northern analysis.

1) Mevalonate prevents apoptosis when co-incubated with lovastatin, or when administered to lovastatin-pretreated cells. 2) Mevalonate restores the lovastatin-arrested cell cycle, allowing S phase entry. 3) Mevalonate does not prevent lovastatin-induced apoptosis after a critical duration of lovastatin pretreatment. For cell lines Daoy and UW228 this was 24 hours, and for D283 Med and D341 Med it was 48 hours. 4) Increases in HMG-CoA reductase mRNA levels induced by lovastatin are abrogated by co-incubation with lovastatin and mevalonate.

These results confirm that lovastatin inhibition of this enzyme results in blockage of the mevalonate pathway, and that such a block is a critical step in the mechanism of lovastatin-induced apoptosis.

Perception of a phantom limb is frequent after an amputation of an upper or lower extremity. Phantom penis is reported infrequently.

Case description and literature review.

The phenomenon of phantom penis followed total penectomy. Several aspects were unusual, particularly the existence with phantom only in the erect state, and associated recrudescence of a preoperative painful ulcer. General features of limb phantoms after amputation are reviewed including a résumé of recent studies of cortical reorganization. The phantom process is analyzed looking for clues to the nature of the underlying neural organization. The puzzle of phantom pain is briefly touched on.

The development of the phantom is attributed to activity in the deafferented parietal sensory cortex.