A simulation model to investigate the impact of cardiovascular risk in renal transplantation.

Premature cardiovascular (CV) disease is the leading cause of death following renal transplantation and, as a consequence of death with a functioning graft, it is a major cause of graft loss. Renal transplant recipients have a high prevalence of CV risk factors that influence both patient and graft survival. We used data on the relationship between CV risk factors and graft and patient survivals to develop a discrete event simulation model to study the possible impact of CV risk factor reduction on transplant outcome. The simulation was based on a renal unit in a population that has the risk factor profile of patients from the West of Scotland. We studied the dynamic between patient numbers on the waiting list compared to the transplanted list. After establishing results pertinent to the renal unit, we investigated in what way potential changes to transplant policy affected patient numbers. These perturbations included changing the number of transplants performed, changing the incidence of acute rejection, and interventional policies where patients on the waiting list were selectively transplanted taking into account their CV risk factor profiles. Overall, the model predicts that reducing CV risk in the population with end-stage renal failure awaiting kidney transplantation will have comparable benefits to foreseeable developments in immunosuppression or attainable increases in transplant numbers. Moreover, addressing CV risk has benefits for all patients regardless of whether or not they ultimately receive a kidney transplant.

Pitfalls in cerebrospinal fluid test for the diagnosis of neurosyphilis.

OBJECTIVE: To determine the usefulness of cerebrospinal fluid tests in the diagnosis of neurosyphilis. METHODS: Two hundred and seven cerebrospinal fluid-Venereal Disease Research Laboratories tests were performed at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia between 1992 and 1997. The records of 14 cases with progressive neurological disease and reactive serum fluorescent treponemal absorbent antibodies or treponemal pallidum hemagglutination test were reviewed for clinical presentation, cerebrospinal fluid analysis and Venereal Disease Research Laboratories, neuro-imaging abnormalities and compatibility with the diagnosis of neurosyphilis. The diagnosis of neurosyphilis was made if the patient had reactive serum fluorescent treponemal absorbent antibodies or treponemal pallidum hemagglutination, history of progressive neurological disease and increased cerebrospinal fluid cells or protein. RESULTS: None of the 207 cerebrospinal fluid-Venereal Disease Research Laboratories tests were reactive. The diagnosis of neurosyphilis was made in 10 out of 14 cases with progressive neurological disease and reactive serum rapid plasma reagin, fluorescent treponemal absorbent antibodies and treponemal pallidum hemagglutination. CONCLUSION: We conclude that if reactive cerebrospinal fluid-Venereal Disease Research Laboratories is required to confirm or diagnose neurosyphilis, most cases will be overlooked.

Pitfalls in cerebrospinal fluid test for the diagnosis of neurosyphilis.

OBJECTIVE: To determine the usefulness of cerebrospinal fluid tests in the diagnosis of neurosyphilis. METHODS: Two hundred and seven cerebrospinal fluid-Venereal Disease Research Laboratories tests were performed at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia between 1992 and 1997. The records of 14 cases with progressive neurological disease and reactive serum fluorescent treponemal absorbent antibodies or treponemal pallidum hemagglutination test were reviewed for clinical presentation, cerebrospinal fluid analysis and Venereal Disease Research Laboratories, neuro-imaging abnormalities and compatibility with the diagnosis of neurosyphilis. The diagnosis of neurosyphilis was made if the patient had reactive serum fluorescent treponemal absorbent antibodies or treponemal pallidum hemagglutination, history of progressive neurological disease and increased cerebrospinal fluid cells or protein. RESULTS: None of the 207 cerebrospinal fluid-Venereal Disease Research Laboratories tests were reactive. The diagnosis of neurosyphilis was made in 10 out of 14 cases with progressive neurological disease and reactive serum rapid plasma reagin, luorescent treponemal absorbent-absorbent antibodies and treponemal pallidum hemagglutination. CONCLUSION: We conclude that if reactive cerebrospinal fluid-Venereal Disease Research Laboratories is required to confirm or diagnose neurosyphilis, most cases will be overlooked.

Transcranial magnetic stimulation in Behçet's disease: a cross-sectional and longitudinal study with 44 patients comparing clinical, neuroradiological, somatosensory and brain-stem auditory evoked potential findings.

OBJECTIVES: To compare neurological involvement in Behçet's disease as documented by transcranial magnetic stimulation (TMS) with clinical, neuroradiological, somatosensory (SEP) and auditory evoked potential (BAEP) findings. METHODS: Forty-four patients were studied over an 8 year period. Nine patients had follow-up studies done. TMS central motor conduction (CMC) studies to upper and lower limb muscles, brain magnetic resonance imaging (MRI), SEP, and BAEP testing were conducted. RESULTS: Thirty-nine patients had CMC slowing, decreased amplitude or absent motor evoked potentials (MEP); 5 of these patients were neurologically normal. Concordance of TMS results, clinical deficits, and MRI findings occurred in 36 of the 39 patients. SEP and BAEP testing proved non-complementary to MEP. Generally, follow-up studies revealed faster CMC and higher MEP amplitude. However, in two patients the CMC time to one target muscle became prolonged with diminished MEP amplitude over a period of 1.5-3 years. CONCLUSIONS: TMS can be useful in detecting and quantifying motor tract dysfunction in Behçet's disease and provides functional information complementary to imaging studies. TMS is more sensitive than either SEP or BAEP. Our longitudinal studies suggest that TMS studies may be valuable in monitoring disease activity or therapeutic response.

Hemiplegia caused by inadvertent intra-carotid infusion of total parenteral nutrition.

A 24 year-old woman developed acute hemiplegia and a seizure following accidental catheterization of the right common carotid artery and total parenteral nutrition infusion. Magnetic resonance imaging of the brain showed lesions in the frontal lobe and putamen consistent with an ischemic stroke. Angiography through the central venous catheter confirmed its intra-arterial location. The patient's weakness improved after hyperbaric oxygen treatment. We concluded that stroke or seizures during total parenteral nutrition administration through a central venous catheter should alert one to the possibility of inadvertent intra-arterial infusion, especially in patients who have had central lines inserted several times previously.

Acute Wernicke's encephalopathy associated with hyperemesis gravidarum: magnetic resonance imaging findings.

A 25-year-old woman with hyperemesis gravidarum developed acute Wernicke's encephalopathy during prolonged intravenous fluid therapy without vitamin supplements. Delay in diagnosis led to a persistent severe neurological deficit, including coma. Gadolinium-diethylenetriaminepentaacetic acid-enhanced magnetic resonance imaging revealed symmetrical lesions around the aqueduct and fourth ventricle, which resolved after treatment with thiamine. She did not regain consciousness. This report demonstrates the diagnostic value of enhanced magnetic resonance imaging in acute Wernicke's encephalopathy.

Familial tremulous and myoclonic dystonia with white matter changes in brain magnetic resonance imaging.

We report two families with a disorder, probably autosomal recessive, characterized by tremor of juvenile onset, dystonia, and myoclonus with preserved cognitive, cerebellar, and peripheral nervous system functions. During 4 years' follow-up, mild spasticity appeared. Magnetic resonance imaging (MRI) revealed mild diffuse changes in the white matter. Central conduction times for visual, motor, and sensory systems were all prolonged. Extensive metabolic work-up failed to reveal lysosomal, peroxisomal, mitochondrial, or other metabolic abnormalities.

Multiple spontaneous intestinal perforations from atheroembolism after thrombolytic therapy: a case report.

Atheroembolism after thrombolytic therapy, although rare, is unpredictable and carries a poor prognosis. Early diagnosis is difficult because of the many forms of presentation. A 76-year-old man with no history of atheromatous disease, who had received streptokinase as treatment for myocardial infarction, had lower gastrointestinal bleeding, progressive renal failure and peripheral ischemia. At laparotomy performed when the peritoneal dialysate was found to contain enteric contents, numerous ischemic small-bowel infarcts were seen, many of which had perforated. The entire intestine was involved, and despite efforts to repair the perforations, the patient had a downhill course and died 44 days after admission to hospital. In patients with disseminated atheroembolism after thrombolytic therapy, supportive care is the only treatment currently available. As thrombolytic therapy becomes more common in the treatment of myocardial infarction, greater effort will be needed to provide better treatment for patients with disseminated atheroembolism as a result of thrombolytic therapy.

Myelopathy after intrathecal chemotherapy. A case report with unique magnetic resonance imaging changes.

BACKGROUND: Paraplegia caused by intrathecal chemotherapy has no known pathognomonic features and is a diagnosis of exclusion. METHODS: The authors reported the clinical and neuroimaging findings in one patient with this syndrome. RESULTS: The patient had severe paraplegia with urinary retention and impaired pain and touch sensation below T-10 with sparing of proprioception and vibration sense. Magnetic resonance imaging (MRI) scan showed diminished intensity throughout the central cervical spinal cord. Post-gadopentetate dimeglumine enhancement was scattered throughout the cervical spinal cord and in two areas of the dorsal spinal cord. Axial views of the cervical spinal cord showed that this enhancement was limited to the lateral columns. CONCLUSIONS: The MRI in myelopathy due to intrathecal chemotherapy may show a unique pattern of postgadopentetate dimeglumine enhancement limited to the lateral columns of the spinal cord. However, two recently encountered patients with the same syndrome did not show similar changes.

Bulk diffusion apnea test in the diagnosis of brain death.

OBJECTIVE: To assess the efficacy of bulk diffusion in maintaining oxygenation during apnea testing for brain death. DESIGN: Case series. SETTING: ICU in a primary care hospital. PATIENTS: Twenty-four consecutive patients with suspected brain death. Most patients suffered cerebral trauma from vehicular accidents. INTERVENTION: Patients were preoxygenated with an FIO2 of 1.0 and were maintained during apnea testing with bulk flow of an FIO2 of 1.0 at 40 to 60 L/min in adults and 15 L/min in children. The pre-apnea PaCO2 was between 35 to 45 torr (4.7 to 6.0 kPa) in all patients. MAIN OUTCOME MEASURES: Twenty-three patients completed the test. Five patients had a PaO2 < 100 torr (< 13 kPa) during the 10-min ventilator withdrawal time period. MAIN RESULTS: No patient breathed spontaneously during the apnea test. Twenty-two patients achieved a PaCO2 > 60 torr (> 8 kPa). One patient had a postapnea PaCO2 of 59 torr (7.8 kPa). The test was stopped in one patient who became hypotensive. CONCLUSIONS: The bulk diffusion technique has several advantages, including ease of performance over other methods of supplying oxygen during apnea testing, but this method does not prevent hypoxemia in patients with lung disease.

A rare intrapericardial mass in a neonate.

We describe a rare case of a neonate born with an intrapericardial mass composed of extralobar pulmonary sequestration and a cyst of bronchogenic origin. After an uneventful delivery, this full-term newborn was noted to be grunting and indrawing. He remained tachypneic despite adequate management for bilateral pneumothoraces. Diagnostic studies showed a 3 x 3 x 4 cm diameter cystic lesion in the anterior mediastinum causing posterior-lateral displacement of the superior vena cava. The heart itself was structurally normal. Bronchoscopy and esophagoscopy failed to detect any structural abnormalities. At 3 weeks of age, sternotomy and resection of the lesion was performed. The mass was clearly intrapericardial and consisted of sequestrated pulmonary tissue with a unilocular mucus filled bronchogenic cyst. Small systemic tributaries fed the lesion from the posterior-superior aspect. There was no connection with the heart or great vessels. Postoperative recovery was uneventful.

Neurobrucellosis: clinical and therapeutic features.

Eighteen patients with neurobrucellosis are described. Eleven patients had meningitis alone or with papilledema, optic neuropathy, or radiculopathy. Four patients had meningovascular complications manifested by stroke or intracerebral hemorrhage from a presumed mycotic aneurysm. Two patients had parenchymatous dysfunction, including a child who had a cerebellar syndrome without evidence of direct infection of the central nervous system. One patient presented with polyradiculopathy. Twelve of 16 patients had pleocytosis; none had cell counts greater than 419 x 10(6)/L. Most patients had hypoglycorrhachia and elevated levels of protein in the cerebrospinal fluid (CSF). Results of an agglutination test for Brucella in serum were positive for all patients. Six of 16 patients had positive blood cultures, and four of 14 had positive CSF cultures. Antimicrobial treatment included concurrent administration of two or more of the following drugs: streptomycin, tetracycline (or doxycycline), rifampin, and trimethoprim-sulfamethoxazole. Eleven patients fully recovered. Five patients were left with residual neurological deficits. Four of these patients suffered permanent hearing loss, one of whom also had significant loss of vision in one eye. One elderly senile patient with meningovascular brucellosis remained in a vegetative state despite receiving antimicrobial therapy for 6 months. One patient died due to rupture of a mycotic aneurysm within 7 days of initiation of therapy. One other patient was treated after sustaining an intracerebral hemorrhage, but this patient's condition was diagnosed only after discharge.

Four cases of neuroleptic malignant syndrome.

The neuroleptic malignant syndrome (NMS) is a relatively uncommon, sometimes fatal, idiosyncratic drug reaction usually associated with the administration of neuroleptic drugs. The syndrome is characterized by generalized rigidity, fever, altered consciousness or mutism, tremor, autonomic dysfunction, tachypnea, elevated serum creatinine phosphokinase, leukocytosis and myoglobinuria. We report four cases of NMS; one following levodopa/bromocriptine withdrawal, two related to neuroleptic administration and one following heroin use. There are no previous reports linking heroin to NMS. The syndrome is thought to result from acute dopaminergic blockage or dopamine depletion. Levodopa, bromocriptine or both are recommended as specific treatment for this condition.

Treatment of refractory Parkinson's disease with adrenal medullary autografts utilizing two-stage surgery.

Treatment of refractory PD with autologous adrenal medullary implants utilizing two-stage surgery warrants further investigation. This transplantation technique is associated with prolonged transplant area BBB disruption which may require a change in medical treatment strategies including the withdrawal of peripheral dopa decarboxylase inhibitors and possible intravenous or intraventricular dopamine therapy. Of 5 patients receiving adrenal medullary transplants, 3 have demonstrated varying degrees of clinical improvement which has persisted for the duration of the study. The positive correlation between clinical outcome and caudate function (i.e., 6-fluorodopa PET scans) suggests a positive influence of the transplantation procedure on the diseased striatum. Whether or not the grafted tissue remains viable for an extended period is currently being investigated utilizing 6-FDG-PET studies. Because of the presence of persistent BBB disruption, we surmise that at least viability of implanted fenestrated adrenal medullary capillaries exists. We conclude that this prolonged leakage is the result of the implanted tissue rather than the cavitation procedure as prolonged BBB disruption was not witnessed in a control group of patients with post-traumatic cerebral contusions or in Parkinson's patients subjected to thalamotomies. Whether two-stage surgery results in increased graft viability, and host neuronal sprouting, leading to prolonged clinical improvement and slowing the progression of PD awaits continued longitudinal (greater than 24 months) studies.

Double-blind cross-over placebo controlled study of flunarizine in patients with therapy resistant epilepsy.

Twenty-five patients with long-standing therapy resistant epilepsy were studied in an eight-month double-blind cross-over add-on trial with a daily dose of 15 mg flunarizine. In five patients the seizure frequency decreased 50% or more. The mean seizure frequency reduction in the patients on flunarizine was 35%. Particularly the control of secondary generalized seizures improved. Flunarizine did not significantly alter the plasma levels of the regular anticonvulsant drugs. Minimal adverse side effects were reported equally in the flunarizine and the placebo group. In three patients depressive symptoms improved and two patients became free of postictal headaches. Flunarizine appears to be a safe adjuvant anticonvulsant.

Computed radial-current topography of the brain: patterns associated with the normal and abnormal EEG.

We describe a method for producing estimates of radial-current topography underlying the background EEG. This method is based on the application of the laplacian operator to potentials measured on the scalp using a 31-electrode recording array. The laplacian is applied analytically to a potential surface obtained by bicubic-spline interpolation of the measurements at the electrode sites. The results obtained when the method was applied to the alpha rhythm recorded from a normal volunteer and to the slow wave activity recorded from a neurologic patient are presented. The alpha rhythm is associated with areas of strong radial-current activity in the occipital regions (although dominantly right); for the slow rhythm the activity appears in the medial-frontal region. The radial-current topography for the alpha rhythm suggests rotating dipole generators in the occipital lobes whereas it is suggestive of a radially oriented dipole in the case of the delta activity. Discussion is focused upon the apparent advantages of radial-current topography for localizing brain electrical activity, upon the strengths and weaknesses of the method, and upon the observation that the topography of radial current activity obtained would have been difficult to predict from a visual examination of raw EEG traces alone.

Evolution of visual evoked potentials in optic neuritis.

The visual evoked potential (VEP) latency was either abnormally prolonged or absent in the involved eye of 47 patients with optic neuritis. Twenty-two of these patients with known multiple sclerosis (MS), had similar abnormalities to 25 patients with no clinical evidence of MS. Follow-up clinical assessment and VEP were done 10 to 42 (mean 22) months later in 34 patients. In 15 of 34 patients with no VEP from the involved eye during initial examination, 6 returned to normal, 8 had prolonged latencies and 1 still had no response at follow up. Of 19 patients who initially had prolonged latencies in the involved eye, 6 returned to normal, 11 had prolonged latencies and 2 had no response at follow up. The VEP is helpful in confirming the diagnosis of ON. The examination must be performed when the patient is symptomatic or soon thereafter as 35% of our patients with an abnormal initial VEP had a normal VEP at follow up. This normalization was not related to the severity of the initial VEP abnormality.

Ankylosing spondylitis and multiple sclerosis: an apparent association?

The prevalence of HLA-B27 in 420 patients with multiple sclerosis (MS) was 43 (10.2%). Five of 20 B27 positive patients who were further assessed clinically and radiologically had ankylosing spondylitis (AS), a prevalence of between 12 and 25%, compared with previously established prevalence rates of B27 in members of the normal population of between 1 and 2% Sixteen patients with AS underwent brainstem auditory (BAEP), visual (VEP) and somatosensory (SSEP) evoked potential studies, with only minor, and predominantly peripheral, abnormalities of SSEP, except for one patient who developed MS during the study. Our data lend some support to an association between AS and MS but refute the possibility of a frequent subclinical MS-like syndrome in AS. They show there is unlikely to be any confusion when performing evoked potential studies in patients with AS.

A double-blind study of bromocriptine and L-dopa in de novo Parkinson's disease. Short-term results.

The first phase of a longitudinal multicenter study comparing bromocriptine and L-dopa (as Sinemet) as de novo therapy for Parkinson's disease using a double-blind randomized design has recently been completed. Over a period of 5.5 months, bromocriptine and L-dopa were equipotent in reducing functional and neurological disability. These observations complement and extend earlier studies and suggest a role for bromocriptine as de novo therapy of Parkinson's disease.

Loss of brainstem and pupillary reflexes in amoxapine overdose: a case report.

A case of severe Amoxapine overdose which presented with unusual neurologic signs and from which a complete recovery was attained is discussed.