CALCINOSIS CUTIS - A SERIES OF 59 CONSECUTIVE CASES CONFINED AMONG WOMEN.

BACKGROUND: Calcinosis cutis is the cutaneous deposition of calcium salts. Tumoral Calcinosis is a condition consisting of massive subcutaneous deposits of calcium salts often overlying large joints in otherwise healthy patients. OBJECTIVE: To describe the characteristics of a series of patients with Tumoral Calcinosis in the Gurage Zone of Central Ethiopia. METHODOLOGY: Data was collected from 59 patients who presented with clinical diagnosis of calcinosis cutis around hip region between January 2005 and January 2009. RESULTS: All cases were females, with a mean (standard deviation) age at diagnosis of 50.7(10.8). The duration of illness ranged from one to eighteen years. The cases were distributed in the different villages of Gurage Zone without any sign of clustering of cases. The lesions were localized around hip region on both sides. The patients did not have any related co-morbidity or any history of similar illness among close family members. None of the patients gave history of evident trauma to the site of the lesions. Significant proportion of the patients (53.4%) confirmed to carry water container and/or other goods on their side. Serum Phosphate and Calcium levels in selected patients were with in normal limit. Histo-pathological examinations of five cases revealed Calcium deposits in collagenous connective tissue. CONCLUSION: The lesion was found to be relatively common in the study area and specifically confined to females. The probable factor associated with the cases is carrying objects on their side (hip area). Further research with in-depth clinical and laboratory evaluation is of paramount importance.

Design, methodological issues and participation in a multiple sclerosis case-control study.

OBJECTIVES: This study was conducted to determine whether the risk of developing multiple sclerosis (MS) was associated with certain environmental exposures or genetic factors previously reported to influence MS risk. This paper describes the methodological issues, study design and characteristics of the study population. MATERIALS AND METHODS: Individuals with definite MS were identified from a prevalence study conducted in three geographic areas. The target number of cases was not reached, so an additional study area was added. Identifying clinic controls was inefficient, so controls were recruited using random digit dialing. All study participants completed a detailed questionnaire regarding environmental exposures using computer-assisted telephone interviewing, and blood was collected for genetic analysis. RESULTS: In total, 276 cases and 590 controls participated, but participation rates were low, ranging from 28.4% to 38.9%. Only one-third (33.6%) of individuals identified in the prevalence study agreed to participate in the case-control study. Cases were more likely to be non-Hispanic white and older than their source populations as identified in the preceding prevalence study (P < 0.05). Most participants provided a blood sample for genotyping (91%; n = 789). CONCLUSIONS: Epidemiological studies play a key role in identifying genetic and environmental factors that are associated with complex diseases like MS. Methodological issues arise in every study, and investigators need to be able to detect, respond to and correct problems in a timely and scientifically valid manner.

The role of a maternity waiting area (MWA) in reducing maternal mortality and stillbirths in high-risk women in rural Ethiopia.

OBJECTIVE: To describe maternal mortality and stillbirth rates among women admitted via a maternity waiting area (MWA) and women admitted directly to the same hospital (non-MWA) over a 22-year period. DESIGN: Retrospective cohort study. SETTING: Hospital in rural Ethiopia, which provided comprehensive emergency obstetric care and has an established MWA. POPULATION: All women admitted for delivery between 1987 and 2008. METHODS: Data on maternal deaths, stillbirths, caesarean section and uterine rupture were abstracted from routine hospital records. Sociodemographic characteristics, antenatal care and other data were collected for 2008 only. Rates and 95% confidence intervals were calculated for maternal mortality and stillbirth. MAIN OUTCOME MEASURES: Maternal mortality and stillbirth. RESULTS: There were 24, 148 deliveries over the study period, 6805 admitted via MWA and 17, 343 admitted directly. Maternal mortality was 89.9 per 100, 000 live births (95% CI, 41.1-195.2) for MWA women and 1333.1 per 100, 000 live births (95% CI, 1156.2-1536.7) for non-MWA women; stillbirth rates were 17.6 per 1000 births (95% CI, 14.8-21.0) and 191.2 per 1000 births (95% CI, 185.4-197.1), respectively; 38.5% of MWA women were delivered by caesarean section compared with 20.3% of non-MWA women, and none had uterine rupture, compared with 5.8% in the non-MWA group. For the 1714 women admitted in 2008, relatively small differences in sociodemographic characteristics, distance and antenatal care uptake were found between groups. CONCLUSIONS: Maternal mortality and stillbirth rates were substantially lower in women admitted via MWA. It is likely that at least part of this difference is accounted for by the timely and appropriate obstetric management of women using this facility.

Expression of multiple cytochrome p450 enzymes and multidrug resistance-associated transport proteins in human skin keratinocytes.

Cytochrome P450 enzymes metabolize various endogenous and exogenous small molecular weight compounds. Transport-associated proteins, such as P-glycoprotein, multidrug resistance-associated protein and lung resistance protein are overexpressed in drug-resistant cell lines, as well as in human tumors from various histologic origins, including malignant melanoma. Little is known about the expression and function of cytochrome enzymes and multidrug resistance-associated transport proteins in human skin; therefore, the aim of this study was to analyze the expression pattern of cytochrome enzymes and multidrug resistance-associated transport proteins in proliferating human epidermal keratinocytes under constitutive conditions and after induction with various inducers. Reverse transcription-polymerase chain reaction revealed constitutive expression of cytochromes 1A1, 1B1, 2B6, 2E1, and 3A5 in keratinocytes and showed expression of cytochrome 3A4 after incubation with dexamethasone. The expression of cytochrome 1A1 was enhanced on the mRNA level after induction with benzanthracene. Reverse transcription-polymerase chain reaction analysis of the multidrug resistance-associated transport proteins revealed constitutive expression of multidrug resistance-associated proteins 1 and 3-6, and lung resistance protein in human epithelial keratinocytes and was negative for multidrug resistance 1 and 2. Expression of 1 was seen after induction with dexamethasone. Reverse transcription-polymerase chain reaction results were confirmed by immunoblots which showed expression of cytochromes 1A1, 2B6, 2E1, and 3A, multidrug resistance-associated proteins 1, 3, and 5 as well as multidrug resistance 1 after induction with dexamethasone. Immunohistology showed positive immunofluorescence in skin specimens for cytochromes 1A1, 2B6, 2E1, and 3A and multidrug resistance-associated protein 1 and multidrug resistance 1. Constitutive activity of cytochrome 1A1, 2B, 2E1, and 3A enzymes was measured by catalytic assays. These results show that keratinocytes of the human skin express various transport-associated enzymes and detoxifying metabolic enzymes. Previous studies have revealed that cytochrome enzymes and transport-associated proteins play complementary parts in drug disposition by biotransformation (phase I) and anti-transport (phase III) and act synergistically as a drug bioavailability barrier.

Psychiatric aspects of clinical neurology.

The author assessed 241 inpatients and outpatients on a neurology service for emotional disorders, using a systematic interviewing technique. DSM-III diagnoses were established in 101 of these patients (41.9%). The author presents a descriptive assessment of the patients' emotional disorders as well as data concerning the connections between neurologic and emotional illness.

Sympathoadrenomedullary hyperactivity in the neuroleptic malignant syndrome: a case report.

The authors describe a patient with the neuroleptic malignant syndrome whose excessive catecholamine excretion indicates hyperactivity of the sympathoadrenomedullary component of the autonomic nervous system. Their finding provides a physiological basis for using catecholamine blocking agents to treat some patients with this syndrome.

Antidepressant pharmacotherapy of depression associated with multiple sclerosis.

In a double-blind clinical trial involving 28 patients with multiple sclerosis and major depressive disorder, 14 patients were randomly assigned to a 5-week trial of desipramine and individual psychotherapy and 14 to placebo plus psychotherapy. Clinical judgments indicated that patients treated with desipramine improved significantly more than the placebo group. This was confirmed by scores on the Hamilton Rating Scale for Depression but not by Beck Depression Inventory scores. Side effects limited desipramine dosage in half of the treated patients. The authors conclude that desipramine has a modest beneficial effect in serious depression associated with multiple sclerosis but that side effects may be more of a limiting factor than in patients without medical or neurologic disease.

Association between bipolar affective disorder and multiple sclerosis.

Ten patients from Monroe County, N.Y., had both multiple sclerosis and bipolar affective disorder. Epidemiologic data indicate that the expected number would be 5.4. This difference may indicate an association between these disorders.

Depressive episodes in patients with multiple sclerosis.

Thirty multiple sclerosis patients were assessed: 15 with predominantly cerebral involvement of their demyelinating disease and 15 with predominantly spinal cord and cerebellar involvement. The groups were matched with regard to age, duration of illness, and Kurtzke disability scores. Assessment included neuropsychological testing, the Beck Depression Inventory, and a psychiatric interview patterned after the Schedule for Affective Disorders and Schizophrenia. A group of normal volunteers served as controls for the neuropsychological testing. There were significantly more major depressive episodes in the cerebral group, as assessed by the patients' histories and by interview, and there was a trend toward more depressive symptoms in this group, as measured by the Beck inventory.

Evidence for atypical depression in Parkinson's disease.

The Research Diagnostic Criteria were applied to 16 depressed patients with Parkinson's disease and 20 depressed multiple sclerosis patients. Diagnoses of anxiety and panic disorder were significantly more frequent among the patients with Parkinson's disease. These patients may experience atypical depression.

The spectrum of depression in multiple sclerosis. An approach for clinical management.

Twenty patients with clinically definite multiple sclerosis who experienced major depressive episodes according to Research Diagnostic Criteria are described. The heterogeneous quality of these depressive episodes is presented by categorizing the episodes according to ten Research Diagnostic Criteria depressive subtypes. Four interpersonal management strategies for such patients that are applicable within a neurologic practice setting are described. The most important feature concerning prognosis for these depressive episodes appears to be the relationship between the depressive episode and the underlying demyelinating disease. When depression occurred in the setting of clinically significant disease activity, the outcome was usually favorable.

Affective disorders in multiple sclerosis. Review and recommendations for clinical research.

This review of research on affective disorders in multiple sclerosis was prepared by members of the Cognitive Function Study Group of the National Multiple Sclerosis Society (New York, NY) to call attention to the prevalence and seriousness of emotional disturbances in multiple sclerosis, and to encourage further investigation of these syndromes. We present English-language studies of euphoria, pathological laughing and weeping, depression, and bipolar disorder, describe methodological limitations, and suggest areas for future clinical research.

Behavioral disorders in multiple sclerosis, temporal lobe epilepsy, and amyotrophic lateral sclerosis. An epidemiologic study.

Certain CNS diseases can produce specific behavioral abnormalities. We used a computer search technique to identify all inpatients at Strong Memorial Hospital, Rochester, NY, who had received diagnoses of multiple sclerosis (MS), temporal lobe epilepsy (TLE), and amyotrophic lateral sclerosis (ALS) between 1965 and 1978. We found 368 patients with MS, 402 patients with TLE, and 124 patients with ALS. These groups were matched against the Monroe County (New York) Psychiatric Register to determine patterns of behavioral pathology. Prevalence rates for psychiatric contact were not significantly different between MS and TLE (19.3% v 22.9%), but both were higher than the prevalence rate for ALS (4.8%). When behavioral patterns were assessed, patients with MS demonstrated a significantly higher rate of depressed affective disorders (61.97% of register matches) than patients with the other two diseases. Multiple sclerosis may present a neurologic model for mood disturbance.

Abnormal vitamin B12 metabolism in human immunodeficiency virus infection. Association with neurological dysfunction.

An increased prevalence of vitamin B12 deficiency has been reported in patients infected by the human immunodeficiency virus (HIV). We report an unexpectedly high prevalence (20%) of such abnormal vitamin B12 metabolism in a population of HIV-infected patients referred for neurological evaluation. This abnormality was associated with both peripheral neuropathy and myelopathy. A majority of those treated with cyanocobalamin had a therapeutic response. Selected neuropathological results suggest a relationship between vitamin B12 deficiency and vacuolar myelopathy. Vitamin B12 deficiency may be a frequent and treatable cause of neurological dysfunction in patients with HIV infection.

Multiple sclerosis and affective disorder. Family history, sex, and HLA-DR antigens.

To investigate a possible genetic cause underlying the clinical association between multiple sclerosis (MS) and affective disorder, we studied 56 patients with MS for psychiatric and genetic (family history, sex, and HLA-DR) characteristics. The 2:1 ratio of females to males expected for patients with MS was observed in this sample (40:16), but the excess of females occurred entirely among the 31 MS patients with major affective disorder (27 females and four males). Bipolar probands with MS had significantly more relatives with affective disorder or MS than did unipolar probands with MS. The HLA-DR antigen frequencies in patients with MS categorized by type and family history of affective disorder suggest that it may be possible to validate such clustering of patients. We concluded that sex and other genetic factors are related to the affective symptoms in MS and emphasize the importance of psychiatric evaluation of these patients.

Multiple sclerosis. The problem of incorrect diagnosis.

Various neurologic disorders may be diagnosed incorrectly as multiple sclerosis (MS) since there is no test that is entirely specific for the disease. We report ten patients who met clinical criteria for probable or definite MS and who were given incorrect diagnoses. All of the patients were subsequently shown to have alternative diagnoses, three of which were directly treatable. From these illustrative cases, five characteristics were identified that alerted us to the possibility of an alternative diagnosis. We have called these characteristics "red flags," and suggest that they may be useful as features casting doubt on the diagnosis of MS if used judiciously in conjunction with clinical diagnostic criteria.

A controlled neuropsychological comparison of Huntington's disease and multiple sclerosis.

This study compared the intellectual deficits of patients who had the earliest stages of Huntington's disease (HD) with those of mildly or moderately affected patients suffering from multiple sclerosis; both groups were matched for age, education, and ability to function. Twenty-one HD patients, 30 multiple sclerosis subjects, and 15 matched controls were evaluated neuropsychologically; all were free of psychoactive medications. The two patient groups showed similar overall patterns of impairment, though the HD group had greater verbal and nonverbal memory deficits. The HD patients also demonstrated significant dyscalculia and showed indications of developing problems in language usage and copying. These results are discussed in light of each disorder's neuropathologic substrate.

Incorrect diagnosis of Alzheimer's disease. A clinicopathologic study.

OBJECTIVES: To examine the accuracy of clinical diagnoses of Alzheimer's disease (AD) in subjects enrolled in the Rochester Alzheimer's Disease Project (RADP) who were examined at autopsy, and to present a list of clinical "red flags." DESIGN: Autopsy examination of both prospective and retrospective subjects consecutively enrolled in this clinicopathologic study of the RADP. SETTING: University hospital and research center, using a multidisciplinary geriatric neurology clinic, satellite clinics, nursing home visits, and home visits. PATIENTS: One hundred seventy subjects clinically diagnosed as having AD who were enrolled in the RADP between 1983 and 1993 underwent neuropathologic examination. Of these, 93 had been enrolled prospectively and 77 retrospectively. MAIN OUTCOME MEASURES: Agreement between clinical and pathologic diagnoses. RESULTS: One hundred forty-nine subjects of 170 clinically diagnosed as having AD fulfilled the pathologic criteria for AD, yielding an accuracy rate of 88%. Of 93 subjects enrolled prospectively and diagnosed as having AD, 83 (90%) met the histologic criteria for AD. Of the 77 subjects enrolled retrospectively, neuropathologic examination indicated definite AD in 66 (86%). CONCLUSIONS: There was a high correlation between clinicians' diagnoses and final pathologic diagnoses. The most common clinical errors involved the misdiagnosis of dementias due to Parkinson's disease and cerebrovascular disease. There was no significant difference in the accuracy rates of subjects enrolled prospectively and retrospectively.

Clinical diagnosis of multiple sclerosis. The impact of magnetic resonance imaging and ancillary testing. Rochester-Toronto Magnetic Resonance Study Group.

OBJECTIVE: Magnetic resonance imaging, computed tomography, cerebrospinal fluid analysis, and evoked potential testing are used to assist in the diagnosis of patients suspected to have multiple sclerosis (MS). The impact of these tests on a clinician's diagnosis of patients suspected to have MS has not been studied systematically. DESIGN: Clinicians made a diagnosis of each patient following clinical evaluation, again after reviewing the results of magnetic resonance imaging, and finally after reviewing information from other laboratory testing. These diagnoses were compared with the criterion standard of a masked "gold standard" panel reviewing all information after a mean follow-up of 0.9 year. SETTING: The General Neurology Clinic and Multiple Sclerosis Clinic of the University of Rochester (NY). PATIENTS: A consecutive sample of 62 patients diagnosed as having either possible or probable MS following clinical evaluation. MAIN OUTCOME MEASURE: Changes in diagnostic certainty of clinicians following incremental presentation of new laboratory data and the accuracy of such diagnoses. RESULTS: Clinicians used magnetic resonance imaging findings to diagnose definite MS or to eliminate MS from diagnostic consideration in 44% of cases. In these cases, further laboratory testing did not alter clinicians' decisions. In the remaining 56% of cases, in which magnetic resonance imaging did not lead to a diagnosis of definite MS or eliminate MS from diagnostic consideration, further laboratory testing led to such diagnoses in an additional 13% of cases. Gold standard diagnoses were in agreement with the clinician's assessments. CONCLUSIONS: Magnetic resonance imaging aids in the evaluation of patients suspected to have MS; other subsequent studies (computed tomography, cerebrospinal fluid analysis, and evoked potential testing) have less impact. After all studies are performed, about half of such patients still have a tentative diagnosis.

Neuropsychologic status in multiple sclerosis after treatment with glatiramer.

BACKGROUND: Glatiramer acetate (Copaxone) therapy reduces clinical disease activity in relapsing-remitting multiple sclerosis (MS). OBJECTIVE: To study the effect of glatiramer therapy on neuropsychologic function as part of a randomized, placebo-controlled, multicenter trial. METHODS: Two hundred forty-eight patients with relapsing-remitting MS and mild to moderate disability (Expanded Disability Status Scale score, <5.0) were tested before and 12 and 24 months after randomization to administration of glatiramer acetate, 20 mg/d, or matching placebo. Neuropsychologic tests examined 5 cognitive domains most often disrupted in patients with MS: sustained attention, perceptual processing, verbal and visuospatial memory, and semantic retrieval. RESULTS: Baseline neuropsychologic test performance was similar in both treatment groups and was within normal range, except for impaired semantic retrieval. Mean neuropsychologic test scores were higher at 12 and 24 months than at baseline, and no differences were detected between treatment groups over time. No significant interactions were detected between treatment and either time or baseline impairment. CONCLUSIONS: Our 2-year longitudinal study showed no effect of glatiramer therapy on cognitive function in relapsing-remitting MS. Although it is possible that glatiramer therapy has no effect on cognitive function, the lack of measurable decline in cognitive function in both patient groups for 2 years limits the opportunity for glatiramer to demonstrate a therapeutic effect by minimizing such decline. Emerging treatments for MS should continue to be examined for their effect on cognitive impairment because it can be a critical determinant of disability. A greater understanding of the natural history of cognitive decline in MS is essential for a rational design of these drug trials.