Neurosarcoidosis: Longitudinal experience in a single-center, academic healthcare system.

OBJECTIVE: To characterize patients with neurosarcoidosis within the University of Utah healthcare system, including demographics, clinical characteristics, treatment, and long-term outcomes. METHODS: We describe the clinical features and outcomes of patients with neurosarcoidosis within the University of Utah healthcare system (a large referral center for 10% of the continental United States by land mass). Patients were selected who met the following criteria: (1) at least one International Classification of Diseases Clinical Modification, 9th revision code 135 or International Classification of Diseases Clinical Modification, 10th revision code D86* (sarcoidosis) and (2) at least one outpatient visit with a University of Utah clinician in the Neurology Department within the University of Utah electronic health record. RESULTS: We identified 56 patients meeting the study criteria. Thirty-five patients (63%) were women, and most patients (84%) were white. Twelve patients (22%) met the criteria for definite neurosarcoidosis, 36 patients (64%) were diagnosed with probable neurosarcoidosis, and 8 patients (14%) were diagnosed with possible neurosarcoidosis. A total of 8 medications were used for the treatment of neurosarcoidosis. Prednisone was the first-line treatment in 51 patients (91%). Infliximab was the most effective therapy, with 87% of patients remaining stable or improving on infliximab. Treatment response for methotrexate and azathioprine was mixed, and mycophenolate mofetil and rituximab were the least effective treatments in this cohort. CONCLUSIONS: This is a comprehensive characterization of neurosarcoidosis within a single healthcare system at the University of Utah that reports long-term response to treatment and outcomes of patients with neurosarcoidosis. Our results suggest the use of infliximab as a first-line therapy for neurosarcoidosis.

Neurosarcoidosis in a public safety net hospital: a study of 82 cases.

OBJECTIVE: To characterize clinical presentation, laboratory and imaging data, and treatment outcomes for neurosarcoidosis in an urban safety net hospital. METHODS: The research database of Cook County Health and Hospitals system was queried for all cases of sarcoidosis from 2006 to 2013. These cases plus those identified through a survey of neurology faculty were reviewed and flagged if suspected to be neurosarcoidosis. Data were extracted in a standardized fashion, upon review by two experienced neurologists; patients were classified as definite, probable or possible neurosarcoidosis. Disagreements on classification were resolved by consensus conference. RESULTS: 1706 cases of sarcoidosis were identified, with 82 (4.8%) classified as neurosarcoidosis. The cohort was predominantly African American (89%). Six were classified as definite, 34 as probable, and 42 as possible neurosarcoidosis. Neurosarcoidosis was the presenting symptom of sarcoidosis in 74% of cases. The most common presenting phenotype was myelopathy (21.7%), followed by optic nerve/chiasm involvement (16.0%) and epilepsy (11.3%). The facial nerve was involved in only 2% of cases. Chest x-ray showed abnormalities of sarcoidosis in 43.3% of cases, while chest CT did so in 78.6%. Corticosteroids were the initial treatment in 91% of cases, and outcomes were good in 53% of cases. CONCLUSION: Neurosarcoidosis remains a challenging diagnosis with the majority of patients without a previous diagnosis of systemic sarcoidosis. Chest imaging was supportive of the diagnosis in a majority of patients. Our cohort differs from others in the literature due to a low prevalence of facial nerve involvement. Prospective registry studies are needed.

Jumping Frenchmen, Miryachit, and Latah: Culture-Specific Hyperstartle-Plus Syndromes.

In the late 19th century, jumping (French Canadians in Maine, USA), miryachit (Siberia), and latah (Southeast Asia) were among a group of similar disorders described around the world, each of which manifests as an exaggerated startle response with additional late-response features that were felt by some to overlap with hysteria or tics. The later features following the exaggerated startle reaction variably include mimesis (e.g., echopraxia, echolalia) and automatic obedience. These reaction patterns tended to persist indefinitely in affected individuals. Because of their dramatic stimulus-driven behaviors, affected individuals were prone to be teased and tormented by being repeatedly and intentionally startled. Despite clinical overlap between jumping and Tourette syndrome, these entities are now recognized as distinct: in jumping, the key feature is an abnormal startle response, the abnormal reaction is always provoked, and tics are absent, whereas in Tourette syndrome, the key feature is spontaneous motor and vocal tics, although patients with Tourette syndrome may occasionally also have an exaggerated startle response. These disorders have been conceptualized from anthropological, psychodynamic, and neurobiologic perspectives, with no complete resolution to date. Attempts at treatment have been generally unsuccessful, including attempts with bromization and hypnosis, although anecdotal reports of successful deconditioning have been published. In population groups affected, these disorders are usually considered as behavioral peculiarities and not as diseases per se, and there is no apparent tendency to develop disabling mental illness or neurodegenerative disorders. The genesis of these disorders, their cultural and social components, and their interactions with the presumed underlying physiological substrate need further study. Careful descriptive and analytic epidemiological studies are also lacking for all of these disorders.

Epidemiology of sarcoidosis in Afro-Caribbean people: a 7-year retrospective study in Guadeloupe.

BACKGROUND: There are no reliable epidemiological data on sarcoidosis in the French West Indies, although this disease is known to be more frequent and more severe in Black African-Americans and West Indians. OBJECTIVES: This retrospective study aimed to assess the incidence and prevalence of sarcoidosis in Guadeloupe over a 7-year period and to determine its epidemiological, clinical, and evolutionary characteristics. METHODS: Patients were identified through the computerized databases of the three pathology laboratories and two hospitals on the islands of Guadeloupe. Histologically proven cases of sarcoidosis were selected. All patients were recalled at a single study time-point. RESULTS: A total of 75 patients were identified. These included 44 women and 31 men (sex ratio: 1.4), with a mean ± standard deviation (SD) age of 47 ± 14 years and Fitzpatrick skin types IV-VI. The average incidence was 2.28 per 100,000 inhabitants per year (95% confidence interval [CI] 1.69-3.02). The prevalence of sarcoidosis in 2009 was 21.09 per 100,000 inhabitants (95% CI 16.00-26.18). Most patients (61/71, 85.9%) exhibited multiple organ involvement; the mean ± SD number of organs involved was 2.6 ± 1.1. The initiation of systemic therapy was required in 75.7% of cases. Several lines of treatment were necessary in 41.5% of affected patients. At the study time-point, seven patients were found to have died. Four of these deaths were directly attributable to sarcoidosis (mortality rate: 5.3%). CONCLUSIONS: This epidemiological study on sarcoidosis in Guadeloupe reveals a low incidence of the disease and a high degree of severity as evidenced by the average number of affected organs, the high frequency of extrathoracic organ involvement, the frequent use of corticosteroids, and a mortality rate of 5.3%.

West-African trypanosomiasis in a returned traveller from Ghana: an unusual cause of progressive neurological decline.

West-African trypanosomiasis caused by Trypanosoma brucei gambiense is a rare imported infection presenting with somnolence, lymphadenopathy and wide-ranging neurological symptoms. A 67-year-old Caucasian man presented with a 10-month history of cognitive deterioration, ataxic gait, somnolence and urinary incontinence. His symptoms had progressed more rapidly over the course of a month prior to admission. Serological testing confirmed a diagnosis of West-African trypanosomiasis. The patient was successfully treated with eflornithine and made a good recovery. West-African trypanosomiasis should be considered in the differential diagnosis of unexplained cognitive decline in those with a relevant travel history. If left untreated, the condition is universally fatal.

A prospective study of neurocognitive changes 15 years after chronic inhalant abuse.

AIMS: In a previous study, neurological and cognitive deficits reflecting central nervous system (CNS) disruption from chronic inhalant abuse showed substantial recovery after 2 years' abstinence. Functional recovery was progressive, with recovery rates dependent on the degree of impairment prior to abstinence, and severity and duration of initial abuse. Persistent deficits occurred in those with previous 'lead encephalopathy' from leaded petrol abuse. The current study examined recovery in the same cohort 15 years after baseline. DESIGN: Prospective cohort design. SETTING: Two remote Aboriginal communities in Arnhem Land, Australia. PARTICIPANTS: Using baseline group classifications, 27 healthy controls, 60 ex-chronic inhalant abusers and an additional 17 with previous lead encephalopathy were assessed. MEASUREMENTS: Standard neurological, ocular-motor and cognitive functions and blood lead levels. FINDINGS: Chronic (non-encephalopathic) inhalant abusers showed elevated blood lead levels and abnormal scores on most tasks at baseline. At 2 years' abstinence, blood lead was reduced but remained elevated and most scores had normalized. By 15 years, blood lead and all performance scores were equivalent to healthy controls for this group (P > 0.05). The encephalopathic group was more severely impaired on all scores at baseline and showed little improvement, if any, across all tests after both 2 and 15 years' abstinence. Blood lead for this group declined, and was not significantly different to controls after 15 years. CONCLUSIONS: Some inhalant abusers experience severe and persistent neurological deficits, suggesting irrecoverable damage attributable to lead encephalopathy. In the absence of this encephalopathy long-term abstinence from inhalants may allow recovery of normal brain function.

Race-norming of neuropsychological tests.

Recent studies in the United States indicate that some neurologically intact minority groupings perform well below White Americans on neuropsychological tests. This has sparked the production of race-norms, especially for African Americans, that seek to reduce false positive rates (i.e., neurologically intact individuals misdiagnosed with cognitive impairment) in neuropsychological assessments. There are problems with this enterprise including: possible justification for inferior/superior treatment of different racial groupings; unknown effects on false negative rates (i.e., cognitive deficit misdiagnosed as normal); the overlooking of factors possibly responsible for group racial differences (e.g., acculturation); non-scientific and non-operational definitions of race/ethnic groupings; and an impossibly large number of potential race/ethnic groupings for which to generate race-norms. An alternative approach is to use a single set of combined race/ethnic norms and estimate preexisting neuropsychological skill levels by using individual comparison standards. This alternative has been poorly researched, a situation that needs correcting.

Highly variable neural involvement in sphingomyelinase-deficient Niemann-Pick disease caused by an ancestral Gypsy mutation.

Niemann-Pick disease (NPD), an autosomal recessive disorder resulting from mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene, is subdivided into the acute, lethal neuronopathic type A, and the chronic visceral type B, explained by the different residual activity levels of acid sphingomyelinase (ASMase). An increasing number of reports on intermediate forms, challenging this traditional clinical classification, have described a broad range of neurological manifestations; however genotype-phenotype correlations have been compromised by relatively small sample sizes and/or allelic heterogeneity. Here we present a genetically homogeneous group of 20 Gypsy patients with intermediate NPD, where we observed a surprising diversity of neurological features. All affected subjects were homozygous for the same ancestral mutation, W391G in SMPD1, yet displayed the entire spectrum of phenotypic variation observed previously in unrelated affected subjects of diverse ethnicity and disease-causing mutations, ranging from subclinical retinal involvement to severe ataxia, cognitive deficits and psychiatric disorders. The clinical heterogeneity of W391G homozygotes points to additional factors, beyond SMPD1 and residual ASMase, which determine the localization, extent and severity of neural involvement. The phenotype similarity of affected relatives suggests a possible role of genetic modifying factors. In practical terms, W391 is common in the Gypsy population and the diagnosis of NPD should be borne in mind despite the atypical course of the disease. Generally, our findings indicate that mutation analysis is of limited value in predicting brain damage, and the option of enzyme replacement therapy should be considered in intermediate NPD.

The frequency and profile of neurology in black South African HIV infected (clade C) patients - a hospital-based prospective audit.

AIM: To determine the frequency and spectrum of neurological illnesses in Black South African hospital-based HIV infected (clade C) patients. METHOD: A prospective audit of 506 consecutive HIV infected medical inpatients at the Helen Joseph Hospital, Johannesburg, South Africa. RESULTS: The patients had a mean age of 37 years; a male:female ratio of 1.2:1; a mean CD4 count of 107 cells/ml. Eighty four percent of patients had AIDS defining CD4 counts (less than 200 cells/ml). Seventy five percent of patients had a neurological illness. In 64% the neurological illness occurred in association with a non-neurological (systemic) illness. Eleven percent of patients had an isolated neurological illness. The predominant systemic illness was tuberculosis (TB), occurring with a frequency of 46%. The neurological spectrum in our patients was similar to that described in the literature, (clade B virus data) other than for a greater frequency of infectious illnesses. CONCLUSION: The neurological profile of HIV infection is a function of the environment and the immunological state of the patient (CD4 count) rather than an influence of the clade.

Ethnic variation in disease patterns and health outcomes in systemic lupus erythematosus.

OBJECTIVE: In a single-center multiethnic lupus cohort, to investigate the influence of ethnicity on the prevalence of cumulative renal and central nervous system (CNS) lupus disease and damage, overall end-organ damage, and mortality. METHODS: Clinical features, end-organ damage, and mortality were compared by ethnic origin among patients at a lupus clinic followed prospectively in a longitudinal design over a 32-year period. Statistical analysis to compare demographic features, cumulative disease manifestations, and damage included chi-square test as well as linear, logistic, and Poisson regressions adjusting for disease duration, age at diagnosis, and presence of dialysis and hypertension. Kaplan-Meier and proportional hazard analyses were performed to compare survival. RESULTS: There were a total of 1017 patients: 853 Caucasian, 88 African-Canadian, and 76 Chinese-Canadian. Age at diagnosis was younger and disease duration was shorter for Chinese-Canadians compared to Caucasians, but similar between African-Canadians and Caucasians. There was no significant difference in CNS disease, comparing Caucasians to Chinese-Canadians. However, CNS disease was greater in African-Canadians than Chinese-Canadians. There was no significant difference between ethnic groups in CNS damage. Renal disease was more common in African-Canadians than Caucasians, with no significant difference between Caucasian and Chinese-Canadian patients. Renal damage was more common in African-Canadians and Chinese-Canadians than Caucasians. There was no significant difference in mortality among the 3 ethnic groups. CONCLUSION: In this single referral center cohort study, there was no significant difference in CNS damage or mortality among the 3 ethnic groups. African-Canadians had a higher prevalence of renal disease and damage. Further investigation into other determinants such as genetic predisposition, treatment, and cultural perceptions is needed.

[Neurocysticercosis. An imaging analysis of 35 cases]. / Neurocisticercose. Análise imagiológica de 35 casos.

Neurocysticercosis (NCC) is the most frequent parasitic disease of the central nervous system. Other Portuguese works showed it to be endemic in the north of our country. The purpose of this paper is to aid the characterization of NCC in the geographic area of our Institution. We retrospectively reviewed the findings of computed tomography (CT) in 35 patients with NCC, including 23 adults and 12 children. There was no significant sex predominance in adults, however, in children the female/male ratio was 2. We found important clinical and radiological differences between adults and children. In the pediatric age group, the active forms were characteristically solitary or scarce inflammatory lesions. This radiologic picture was associated with neurologic focal signs. In these cases, a trial with anticysticercoid drugs is important to settle the diagnosis and avoid brain biopsy. Almost all of our cases (94%) were parenchymatous forms. This can be explained, in part, by the limitations of CT in the ventricular and cisternal compartments. Magnetic resonance is the ideal method in these locations. About half our patients (49%) were of African origin, most of them immigrants from the former Portuguese colonies where NCC is endemic.

Neurocysticercosis. Two hundred thirty-eight cases from a California hospital.

Neurocysticercosis is no longer a medical curiosity in the United States. Two hundred thirty-eight patients with neurocysticercosis were studied between 1981 and 1986 at the Los Angeles County-University of Southern California Medical Center, Los Angeles. Presenting signs and symptoms were protean--ranging from a single convulsion to coma and death. Fifty-one patients (21%) presented with an acute increase in intracranial pressure. There were 71 patients who ultimately required a shunting procedure or craniotomy. Presentation, diagnosis, management, and laboratory adjuncts (the role of cysticercosis titers and the electroencephalogram) are discussed. Mortality and morbidity can be reduced by maintaining a high degree of suspicion in populations at increased risk for cysticercosis.