Faculty Bibliography

The aim of the article is to describe the principal findings among patients with M.tuberculosis and M. bovis CNS infection. Mycobacterium tuberculosis is one of the most common infectious agents that cause death and neurological sequelae around the world. Most of the complications of CNS TB can be attributed to a delay in the diagnosis. Unfortunately, there are no specific diagnostic tools to support an early diagnosis. Other prognostic factors different from delay in treatment have not been identified. Clinical, radiological and laboratory characteristics were analyzed retrospectively from the medical files of all the patients admitted with the diagnoses of tuberculosis. Of 215 patients admitted with systemic tuberculosis, 64 (30%) had a neurological infection. Positive cultures were found in 54 (84%) cases, 18 (33%) in the CSF and the rest in other fluids or tissues. Adenosin deaminase (ADA) enzyme determination was more sensitive than M. tuberculosis PCR in the CSF for supporting an early diagnosis. In addition to a later clinical stage and treatment lag, positive CSF cultures (P=0.001) and the presence of M. bovis (P=0.020) were prognostic factors for a worse outcome. Neither older age, the presence of tuberculomas versus meningeal enhancement, or HIV co-infection, was associated to a worse prognosis. The isolation of M. bovis subspecies was more common that previously reported, and it was associated to the development of parenchymal lesions (P=0.032) when compared to M. tuberculosis. In this study, positive CSF cultures for M. tuberculosis and further identifying M. bovis species were additional prognostic factors for worse outcome. Positive cultures in systemic fluids other than CSF, even when the patient had no obvious systemic manifestations, and ADA determination in the CSF were noteworthy diagnostic tools for the diagnosis.

BACKGROUND:Multiple sclerosis (MS) is a demyelinating disease seldom included in the differential diagnosis of leukoencephalopathy in HIV-positive patients. METHODS:We describe the clinical findings and laboratory results of a 43-year-old male with HIV infection and MS, and reviewed 11 more cases reported in the literature. RESULTS:The first episode of MS occurred either during or after the recognition of the HIV infection except in the few cases reported in 1989. There has been a very strong male predominance. Age at onset was between 30 and 40 years old. The most common clinical course was relapsing and remitting. Most of the cases had a normal CD4+ cell count, usually exceeding 500 cells/mm(3). Despite that CD4+ cell counts were invariable high, all the patients had multiple tests to rule out opportunistic infections and HIV-associated illness. The clinical suspicion of MS was only considered after ruling out other opportunistic infections and was supported with brain imaging showing multiple white matter evanescent lesions, the presence of black holes, and a high myelin basic protein titer in the CSF. CONCLUSIONS:MS is usually considered late in patients with HIV. A typical MS course with suggestive MRI lesions and absence of severe immune suppression should suggest the diagnosis. It is possible that as with other MS patients, earlier initiation of specific treatments for MS will prevent the high burden of the disease and disability in these patients, but stronger evidence for specific recommendations remains to be obtained.

The subacute spongiform encephalopathies are prion diseases characterized by acute and rapid neurodegeneration that lead to the death of the patient within months to a few years. The epidemiology of CJD is complicated and the frequency in Mexico is unknown. We aim to describe the cases of prion disease in Mexico. Consecutive patients who met the diagnostic criteria by the WHO were enrolled. We describe 26 patients with clinical manifestations, imaging and laboratory studies compatible with prion disease. The mean age at onset was 52 years old. The main clinical manifestations were cognitive alterations (69%) followed by extrapyramidal movements (50%), abnormal cerebellar function (46%), behavioral alterations (46%), myoclonus (46%), and mood depression (23%), among other features. Half of the patients progressed rapidly to a state of akinetic mutism (53%). Only 2 (7.6%) patients had a family history of a similar disease. Time interval between onset and diagnosis varied between 71 days to 24 months, with a median of 6 months. The classical bilateral basal ganglia hyperintensities were present in the very early stage of the disease. Protein 14-3-3 immuneassay in the CSF was positive in all measured cases. Bilateral basal ganglia hyperintensities was the most important early finding, while protein 14-3-3 was a late finding and the results were usually obtained after the patient was discharged. Around 1.5 cases of CJD cases per year are reported in our country. When suspected, MRI can support the diagnosis earlier than other studies.

OBJECTIVE:To describe a case of a young adult with severe H1N1 influenza illness associated with hypothalamic abnormalities and post-influenza parkinsonism. DESIGN/METHODS:Case report. PATIENT/METHODS:A 22-year-old woman with H1N1 influenza infection developed encephalopathy followed by diverse hypothalamic dysfunction manifestations, sleeplessness, and persistent parkinsonian features. RESULTS:CSF analysis, brain imaging and EEG ruled out hypoxic brain injury or other illnesses. CONCLUSIONS:A number of viruses have been associated with both acute and chronic parkinsonism. A link between parkinsonism and influenza viruses is somewhat controversial. This is the first reported case of parkinsonism following an H1N1 influenza infection.

The most common neurological manifestation of Cryptococcus neoformans infection is meningitis. Other less common manifestations include parenchymal central nervous system (CNS) granulomatous disease, hydrocephalus and stroke. C. neoformans is often suspected in immunodepressed patients, but it can be easily overlooked in otherwise healthy patients. This paper provides a detailed clinical description of a patient without immunosupression who developed multiple simultaneous neurological manifestations after the infection with C. neoformans.

BACKGROUND:In the pre-highly active antiretroviral therapy (HAART) era, distal sensory polyneuropathy (DSP) was associated with markers of advanced HIV infection and the use of neurotoxic antiretrovirals (ARVs). As HAART became widespread, and the AIDS epidemic shifted into minority populations, the risk factors for DSP became less clear. We explore the roles of ethnicity and ARV in the development of DSP in an HAART era cohort. METHODS:Data from 336 HIV-positive adults were obtained from the Manhattan HIV Brain Bank. One hundred four participants had no DSP at entry visit; at least 1 follow-up visit; and a self-identified ethnicity of non-Hispanic white, Hispanic, or African American. RESULTS:Fifty percent of participants developed DSP; of those, 67% were symptomatic. Participants who developed DSP were older (P = 0.02) and had higher CD4 counts (P = 0.001). ARV-DSP was more common in Hispanics (P = 0.02) and intravenous drug users (P = 0.02). There was a trend for higher pain scores in Hispanics with symptomatic DSP (P = 0.08). CONCLUSIONS:This study suggests that there are ethnic disparities in the clinical manifestations of HIV-related neuropathies including pain and the susceptibility to ARV-DSP. Further studies of larger cohorts are indicated to explore the etiology of these differences.

Distal sensory polyneuropathy (DSP) is the most common neurologic complication of HIV infection and a major cause of morbidity in HIV-infected patients. DSP may occur secondary to HIV (HIV-DSP) or be due to antiretroviral drug toxicity. Timely detection of the symptoms and signs of DSP in patients who have HIV may allow for the reversal of the toxic effects of antiretrovirals and for the initiation of symptomatic treatment. The pathogenic mechanism of HIV-DSP is likely multifactorial. Restorative therapies for DSP are not currently available but recent advances have led to novel symptomatic therapies. This article highlights the risk factors, pathogenesis, pathology, clinical features, diagnostic studies, differential diagnosis, and treatment of HIV-associated neuropathy.

BACKGROUND:Intracerebral hemorrhage (ICH) is an unusual but serious complication of bleeding disorders. ICH is believed to follow thrombocytopenia, alterations in coagulation, and vascular fragility. Information regarding its distribution is nonconclusive, and the mechanism of bleeding is not fully understood. The aim of this study was to examine the clinical and neuroimaging features of ICH in patients with bleeding disorders to predict risk factors for this condition. METHODS:All cases of ICH diagnosed from 1987 to 2004 were retrospectively identified using the centralized database of our institution. Cases were included whenever ICH was caused by a primary hematologic disorder. The clinical characteristics, neuroimages, and outcome were analyzed. RESULTS:A total of 31 patients were identified. ICH was the initial presentation of the bleeding disorder in 9 patients. Overall, 71% had systemic bleeding concurrent to the ICH. All patients had altered mental status. In 45.2% of the patients simultaneous intracranial hemorrhages were found. Eight patients had recurrent ICH. Severe thrombocytopenia (platelet count < 10,000/mm(3)) was present in 41% and very low platelets (</=1000/mm(3)) in 3%. Death occurred in 71%. CONCLUSIONS:Multiple ICH is not an unusual presentation in patients with primary bleeding disorders developing brain hemorrhage. Although low platelet counts can be blamed for the bleeding, factors different from thrombocytopenia should be considered as the principal mechanism. The best predictor of cerebral bleeding is the presence of systemic bleeding.

OBJECTIVE:To evaluate the frequency of and risk factors for epileptic seizures in patients with systemic lupus erythematosus (SLE) in a large cohort series. METHODS:One thousand two hundred patients with SLE were analyzed. The type and frequency of risk factors for seizures associated with SLE were studied and compared with two other series reported in the literature. RESULTS:One hundred and forty-two patients had seizures. Seventy-five patients were studied with a mean follow-up of 5 years from the first seizure episode. Fifty-eight (77%) patients had tonic-clonic seizures, 9 (12%) complex partial seizures (PS), 5 (7%) simple partial motor seizures and 3 (4%) secondary tonic-clonic seizures. In 41 (54%) patients, the seizures occurred within the first year of the SLE diagnosis. Recurrence occurred in 40 (53%) patients, and was associated with PS in 14 (35%; p = 0.006) and time of seizures with SLE onset in 5 (12.5%; p = 0.05). Less than one third of the patients had positive antiphospholipid antibodies. A concurrent infection was present in 16 (21%) patients. CONCLUSIONS:Epileptic seizures were more common during the first year after SLE diagnosis. Neither infection nor antiphospholipid syndrome was associated with the occurrence of seizures.

Peripheral nerve disorders are frequent complications of HIV disease. Distal symmetrical polyneuropathy (DSP) is the most common peripheral nerve disorder associated with HIV and occurs in over one third of infected patients but may occur in up to 67% if asymptomatic patients are included. Risk factors for DSP include increased age, advanced HIV disease, and history of "d-drugs" or other neurotoxic drugs. The primary manifestations of polyneuropathy are slowly progressive numbness and paresthesias, with burning sensations in the feet usually in a symmetrical pattern. The etiology of HIV-associated DSP is unknown, although neurotoxic effects of cytokines, toxicity of HIV proteins, and mitochondrial damage have been implicated. The current treatment for HIV-associated DSP is symptomatic, with pain modifying medications, including anti-inflammatory agents, opioids, antidepressants, antiepileptics, topical anesthetics, and capsaicin. Sustained virologic control may improve DSP. Novel therapies such as -acetyl-l-carnitine or neurotrophic factors are being studied for treatment of DSP.