Modulation of brain dead induced inflammation by vagus nerve stimulation.

Because the vagus nerve is implicated in control of inflammation, we investigated if brain death (BD) causes impairment of the parasympathetic nervous system, thereby contributing to inflammation. BD was induced in rats. Anaesthetised ventilated rats (NBD) served as control. Heart rate variability (HRV) was assessed by ECG. The vagus nerve was electrically stimulated (BD + STIM) during BD. Intestine, kidney, heart and liver were recovered after 6 hours. Affymetrix chip-analysis was performed on intestinal RNA. Quantitative PCR was performed on all organs. Serum was collected to assess TNFalpha concentrations. Renal transplantations were performed to address the influence of vagus nerve stimulation on graft outcome. HRV was significantly lower in BD animals. Vagus nerve stimulation inhibited the increase in serum TNFalpha concentrations and resulted in down-regulation of a multiplicity of pro-inflammatory genes in intestinal tissue. In renal tissue vagal stimulation significantly decreased the expression of E-selectin, IL1beta and ITGA6. Renal function was significantly better in recipients that received a graft from a BD + STIM donor. Our study demonstrates impairment of the parasympathetic nervous system during BD and inhibition of serum TNFalpha through vagal stimulation. Vagus nerve stimulation variably affected gene expression in donor organs and improved renal function in recipients.

Clinical benefit of a short term dietary oatmeal intervention in patients with type 2 diabetes and severe insulin resistance: a pilot study.

AIMS/HYPOTHESIS: To evaluate the potential effectiveness of 'carbohydrate days' as a dietary intervention to overcome insulin resistance in type 2 diabetes. MATERIALS AND METHODS: Patients (n=14) with uncontrolled type 2 diabetes and insulin resistance as defined by a dosage of more than 1 IU/day (*)kg BW were consecutively enrolled in this prospective study. Primary outcomes were daily insulin requirement and mean blood glucose levels which were evaluated before, after, and 4 weeks after the intervention. RESULTS: All patients had a metabolic syndrome, 75% had microvascular and 57.1% macrovascular complications. Hospital setting and diabetes adapted diet alone led to improved glycemic control with a mean blood glucose 158+/-47 mg/dl. Intervention with two days of oatmeal diet further decreased mean blood glucose to 118+/-37 mg/dl (p<0.05). This was associated with a significant reduction of insulin dosage by 42.5% (before: 145+/-68.9 U/d, after 83+/-34.2 U/d, p<0.001) as well as a significant reduction (-26.4%, p<0.01) of serum leptin levels. After the four weeks outpatient period, insulin dosage remained significantly decreased (83+/-20.2 U/kg (*)d, p<0.01). Glycemic control was comparable (mean blood glucose141+/-20.78 mg/dl) to glucose levels within the hospital setting. Adiponectin levels increased significantly by 53.8% (p<0.05). CONCLUSIONS: In this uncontrolled pilot study, hospital admission and diabetes adapted diet followed by oatmeal intervention achieved a approximately 40% reduction of insulin dosage required to achieve controlled glucose levels. This effect was conserved after a 4 week outpatient phase with normal diet.

Downbeat nystagmus with magnesium depletion.

Two patients with neurological signs of magnesium depletion complained of oscillopsia and manifested downbeat nystagmus. Serum magnesium levels measured less than 1.0 mg/dL. Hypomagnesemia resulted from debilitating intestinal disease in both patients and apparently was aggravated in one case by failure to add magnesium sulfate to the patient's regimen for total parenteral nutrition. Neither patient had any of the neurological conditions reported with downbeat nystagmus. Thus, downbeat nystagmus in the primary position occurs with the metabolic derangement of severe magnesium depletion. Another apparent metabolic cause of downbeat nystagmus is thiamine deficiency. Downbeat nystagmus also may occur from a partial deficiency of the metabolic cofactors, magnesium and thiamine.

Midbrain corectopia.

Intermittent corectopia was recently observed in a patient with bilateral, rostral midbrain infarction. Results from neuropathologic examination disclosed isolated but intact Edinger-Westphal nuclei. An explanation of midbrain corectopia centered on segmental innervation of the pupil by the Edinger-Westphal nucleus. In the presence of a paralyzed dilator muscle, select, central inhibition of sphincter tone resulted in an oval and eccentric pupil.

Amaurosis fugax from disease of the external carotid artery.

Three patients with proved internal carotid artery occlusion and diseased external carotid artery or common carotid artery had amaurosis fugax. Evidence for retinal embolization through external carotid collaterals is retinal emboli and infarction after carotid artery manipulation, amaurosis during external carotid angiography, and relief of amaurosis by endarterectomy of this vessel. The abundance of external carotid collaterals, their size, and natural incidence are discussed. Reports clinically support embolization to the central retinal artery and ophthalmic artery through these collaterals.

Parainfectious optic neuritis. Report and review following varicella.

Severe loss of vision and bilateral optic disc edema occurred in a 10-year-old girl 38 days after the rash of varicella first appeared and subsequent encephalitis developed. Recovery of visual function was nearly complete, but optic atrophy persisted. Parainfectious optic neuritis following other viral infections, with the exception of herpes zoster, has a similar clinical profile: delayed onset, severe visual loss, optic disc edema, bilaterality, good recovery, and residual optic atrophy. Conduction delays in our patient's patterned visual evoked potentials implicated demyelination within the optic nerves. The often favorable recovery, frequency of delayed onset, and bilateral involvement of the optic nerves support an autoimmune process in the pathogenesis of parainfectious optic neuritis.

Micromethod for detection of oligoclonal IgG in unconcentrated CSF by polyacrylamide gel electrophoresis.

A micromethod to detect oligoclonal IgG from 50 microL of unconcentrated CSF was developed by using polyacrylamide gel electrophoresis in sodium dodecyl sulfate (SDS-PAGE). Of 17 patients with multiple sclerosis, oligoclonal bands were demonstrated in 16 instances (94%) by micro-SDS-PAGE and in 13 (76%) by agarose gel electrophoresis. The corresponding figures among 30 patients with optic neuritis were 16 (54%) and five (17%), respectively, and among ten patients with other neurological disease the figures were two (20%) and none, respectively. Thus, micro-SDS-PAGE is more sensitive than agarose gel electrophoresis for detection of oligoclonal IgG. The small volume of unconcentrated CSF that is required enhances the usefulness of this test.

Microangiopathy of the brain and retina.

Two women (26 and 40 years old) developed an unusual microangiopathy that affected the brain and retina. Psychiatric symptoms initially overshadowed the subacute features of the progressive neurologic disorder. Ophthalmoscopic findings of multifocal branch retinal artery occlusions provided clinical evidence of vasculopathy. Laboratory data did not reveal evidence of the known vasculitides, including systemic lupus erythematosus (SLE) and syphilis. Cerebral angiography suggested vasculitis in the younger patient. Brain biopsy in the older patient (after 3 months of steroid therapy) revealed a sclerosis of the small pial and cortical vessels that was consistent with a "healed" angitis. Both patients seemed to respond to steroid therapy.

Acute thalamic esotropia.

Three men developed acute esotropia, stupor, and impaired upward gaze. Vestibulo-ocular stimulation showed that the adducted eye remained immobile while the fellow eye responded normally. The alteration of consciousness, the long-tract neurologic signs, and the esotropia quickly resolved. Upgaze paresis and brief bursts of convergence-retraction nystagmus were the major residual signs. Imaging techniques demonstrated lesions of the contralateral posterior thalamus in each patient. Several mechanisms are proposed to explain the acute esotropia. Impairment of monocular projections in the contralateral posterior thalamus could disinhibit neurons in the oculomotor complex, or ischemia of inputs to neurons involved with vergence control in the midbrain could result in tonic activation of the medial rectus. The clinical and radiographic findings are consistent with infarction in the territory of penetrating branches of the basilar-communicating (mesencephalic) artery. Embolism to the top of the basilar artery is presumed to be the precipitating event.

Delayed sequelae of vertebral artery dissection and occult cervical fractures.

We report three patients who developed delayed (ie, more than a week after the injury) symptoms of vertebrobasilar ischemia following motor vehicle accidents. The patients all had angiographic evidence of vertebral artery dissection and, upon further evaluation, occult fractures of the second cervical vertebra that were not detected by simple cervical spine radiography and required polytomography or CT for diagnosis. Vertebral artery dissection can result from occult cervical spine fractures and may present with delayed symptoms of brain ischemia.

Post-traumatic midbrain tremors.

We report 3 patients with post-traumatic tremor and describe the characteristics of the tremor and accompanying neurologic signs. Radiographic and pathologic examination indicated a contralateral midbrain localization of the lesion. The tremor responded to anticholinergic or dopaminergic therapy.

Ventriculostomy for hydrocephalus in cerebellar hemorrhage.

In a matter of hours the neurologic status of two hypertensive patients deteriorated to coma. Cranial computed tomography (CT) showed mild to moderate cerebellar hemorrhage and secondary hydrocephalus. Ventriculostomy resulted in clinical improvement within 20 minutes and obviated the need for suboccipital craniectomy. Both patients made a very satisfactory recovery. Similar patients have occasionally been observed by others. Ventriculostomy should be considered for patients with cerebellar hemorrhage who have hydrocephalus by CT scan and undergo progressive neurologic deterioration. Because the frequency of improvement and the risk of upward cerebellar herniation following ventriculostomy is unknown, immediate surgical evacuation of the hemorrhage should be anticipated.

Chlordecone intoxication in man. I. Clinical observations.

Industrial overexposure to chlordecone, an organochlorine insecticide, caused tremor in 76 of 148 exposed workers. Chlordecone was absorbed through oral, respiratory, and dermal routes, the last possibly the most significant. Epidemiology of this incident disclosed low-level, widespread environmental exposure of man to chlordecone. In 23 workers with chronic chlordecone intoxication, tremor was associated with opsoclonus, pleuritic pain and arthralgia. No seizures were reported. The site of action of chlordecone on the central nervous system is unknown. It concentrates in human adipose and hepatic tissue but is not biodegradable, either in humans or elsewhere in nature.

Psuedotumor cerebri and insecticide intoxication.

Three patients with headache and increased intracranial pressure had elevated blood, serum, and adipose levels of the organochlorine insecticide chlordecone (Kepone). These patients were among 23 employees who suffered from chronic chlordecone intoxication resulting from industrial exposure. In our three patients, investigations eliminated an intracranial mass or other known causes of psuedotumor cerebri. In all three patients, the capacity for cerebrospinal fluid (CSF) absorption was assessed by graded infusions into the subarachnoid space, and was found to be impaired even when papilledema was minimal.

Sarcoid optic neuropathy.

Three patients presented with unilateral progressive optic neuropathy. None of these patients had signs of symptoms referable to the chiasm or eye, thus confining their decline in vision to the optic nerve. Clinical and neuroradiographic evidence suggested a meningioma involving the optic nerve at the orbital-canalicular junction in one patient and the intracranial optic nerve in another patient. Surgical exploration in both patients, however, revealed a noncaseating granuloma. Decline in vision from granulomatous invasion of the retrobulbar optic nerve is an uncommon manifestation of sarcoidosis. Review of our patients' findings suggests that a nonsurgical diagnosis of sarcoid optic neuropathy may have been tenable.

MRI in Lhermitte-Duclos disease.

Lhermitte-Duclos disease (LDD) is a disorder sometimes referred to as a dysplastic gangliocytoma of the cerebellum. This is a focally indolent growth of the cerebellar cortex in which the folia enlarge due to a profusion of dysplastic cortical neurons and a thickening of the molecular layer. Loss of Purkinje cells and thinning of medullary white matter results. The enlarged folia lose their secondary foldings and asymmetrically expand the cerebellar hemisphere. These morphologic features produce a characteristic pattern on some CTs and all MRIs, affording an opportunity for a preoperative diagnosis. MRI of a pathologic specimen suggested that the abnormal T1 and T2 signals corresponded to the atrophic folial white matter, thickened granule cell layer, and outer molecular layer. Because of inherent Hounsfield artifact in posterior fossa with CT, MRI is the imaging modality of choice, with better visualized striated pattern. The uniqueness of these imaging features obviates the need for an obligatory biopsy for asymptomatic patients and either permits more definitive planning for surgical decompression or, in restricted lesions, guides more assuredly complete excision of the cerebellar mass.

Ischemic optic neuropathy: a complication of cardiopulmonary bypass surgery.

Ischemic optic neuropathy followed cardiopulmonary bypass surgery in the postoperative period in 7 of 7685 consecutive procedures. Th visual loss was unilateral in four patients and bilateral in three and there was little improvement. This ischemic infarction of the optic nerve disk was attributed to hypotension, hypothermia, and activation of certain complement factors by the bypass procedure.

Characterization of plasma acylcarnitines in patients under valproate monotherapy using ESI-MS/MS.

OBJECTIVES: The effect of administration of the antiepileptic drug valproate (VPA), on the composition of the plasma acylcarnitine profile (including free carnitine) was investigated. DESIGN AND METHODS: Plasma samples were obtained from 18 individuals (13 males:5 females; 15-65 y) on long-term treatment with VPA (resulting in plasma levels of 14.6-135.0 mg/L; therapeutic conc.: 40-100 mg/L). Acylcarnitines (AC) in plasma were quantified by electrospray tandem mass spectrometry (ESI-MS/MS). RESULTS: VPA was found to increase the levels (mean +/- SD, microM) of 3-hydroxy-isovalerylcarnitine (0.10 +/- 0.04; controls: 0.02-0.06), C14:2 acylcarnitine (0.11 +/- 0.05; controls: 0.02-0.08), propylglutarylcarnitine (0.06 +/- 0.05; controls: 0.00-0.04), and C18-0H-acylcarnitine (0.09 +/- 0.05; controls: 0.00-0.04). The free carnitine (C) (42.2 +/- 9.0; controls: 22.3-54.9) and the total carnitine (52.3 +/- 10.1; controls: 26.5-73.6) were not significantly altered by VPA. Other AC (C2-C18, monounsaturated and hydroxylated) were all within the control range and especially no increase of C8 (valproyl) carnitine was observed. A positive correlation was found between the ratios [AC] / [C] (p < 0.05) or [long-chain AC (C10-C18)] / [C] (p < 0.09) with the plasma VPA concentration. CONCLUSIONS: The unequivocal increase in 3-hydroxy-isovalerylcarnitine is consistent with the increase of 3-hydroxy-isovaleric acid observed in urine of VPA treated patients. This finding suggests an interaction mechanism of VPA with specific enzymes, namely involved in leucine metabolism. Adult patients under VPA monotherapy do not suffer from carnitine deficiency; the effect of the accumulating acylcarnitines is ill-defined.

Light-induced amaurosis fugax.

PURPOSE: To describe an important symptom of bilateral amaurosis precipitated by exposure to bright light. METHODS: Case report. Clinical analysis of transient, painless, asymmetrical visual loss occurring in bright light in a 54-year-old man. RESULTS: Carotid ultrasound showed bilateral carotid disease. Carotid angiography demonstrated occlusion of the left internal carotid artery and severe stenosis of the right internal carotid artery and both external carotid arteries. Visual symptoms and an abnormal photostress test completely remitted after a right carotid endarterectomy. CONCLUSION: Light-induced amaurosis is an unfamiliar manifestation of ocular ischemic syndrome occurring with severe, often bilateral, carotid artery disease. Its recognition is important because the complaint is associated with severe carotid occlusive disease and recognition is necessary for timely surgical intervention because of the major risk for stroke.

Anterior ischemic optic neuropathy with internal carotid artery occlusion.

We examined three patients who had anterior ischemic optic neuropathy and ipsilateral internal carotid artery occlusion. Each patient had transient cerebral ischemic attacks associated with the occluded carotid artery. In two patients there attacks were in temporal proximity to the anterior ischemic optic neuropathy. Carotid angiography showed retrograde filling of the ophthalmic artery through the external carotid artery demonstrating altered perfusion and, perhaps, hypoperfusion of the distal optic nerve head.