Phenotype in parkinsonian and nonparkinsonian LRRK2 G2019S mutation carriers.

OBJECTIVES: Using a family study design, we describe the motor and nonmotor phenotype in probands with LRRK2 G2019S mutations and family members and compare these individuals to patients with idiopathic Parkinson disease (iPD) and unrelated controls. METHODS: Probands with G2019S mutations and their first-degree relatives, subjects with iPD, and unrelated control subjects were identified from 4 movement disorders centers. All underwent neurologic examinations and tests of olfaction, color vision, anxiety, and depression inventories. RESULTS: Tremor was more often a presenting feature among 25 individuals with LRRK2-associated PD than among 84 individuals with iPD. Subjects with LRRK2-PD had better olfactory identification compared with subjects with iPD, higher Beck Depression Inventory scores, and higher error scores on Farnsworth-Munsell 100-Hue test of color discrimination. Postural or action tremor was more common among 29 nonmanifesting mutation carriers compared with 53 noncarriers within the families. Nonparkinsonian family members had higher Unified Parkinson's Disease Rating Scale motor scores, more constipation, and worse color discrimination than controls, regardless of mutation status. CONCLUSIONS: Although tremor is a more common presenting feature of LRRK2-PD than iPD and some nonmotor features differed in degree, the phenotype is largely overlapping. Postural or action tremor may represent an early sign. Longitudinal evaluation of a large sample of nonmanifesting carriers will be required to describe any premotor phenotype that may allow early diagnosis.

The role of glucocorticoid pulse therapy in pulmonary involvement in leptospirosis.

OBJECTIVES: This study discusses incidence and clinical profile of pulmonary involvement in leptospirosis in South Gujarat. It also tries to evaluate the effect of high dose glucocorticoid pulse therapy (GPT) on it. METHOD: A study was carried out on hundred and two patients of suspected leptospirosis, referred to Government Medical College, New Civil Hospital, Surat between June 99 to September 99. The incidence, clinical profile, and specific investigations were studied in patients having pulmonary involvement. Some of the patients were given high dose glucocorticoid pulse therapy. Their outcomes were compared with those who had not been given glucocorticoid pulse therapy. RESULTS: Out of seventy seven seropositive patients 13 (16.8%) developed pulmonary involvement. Mortality was two out of eight patients in the group that received GPT and four out of five patients in the group that did not receive GPT. Two patients who died in the steroid treated group received the drug after 12 hours of onset of dyspnea. CONCLUSIONS: High dose GPT should be given as early as possible after the onset of dyspnea to all the patients with pulmonary involvement in leptospirosis. Further studies are required to establish the GPT as a standard regimen in treatment of pulmonary involvement in leptospirosis.

Autoimmune disorders of the ovary.

Infertility and ovarian disorders may occur not only due to imbalance in the steroid hormones but also due to the alteration in the immune function. A number of autoimmune disorders of the ovary, such as polycystic ovarian syndrome, premature ovarian failure and autoimmune oophoritis, have been documented. Both the cell mediated and humoral immune responses play an important role in these disorders. Cytokines secreted by the immune cells could have an adverse effect on ovarian steroidogenesis whereas the production of pathogenic T cells could lead to autoimmune disease of the ovary. Autoantibodies to granulosa and theca cells as well as zona pellucida of the oocyte have also been documented in women indicating that autoimmunity plays an important role in infertility. Thus the endocrine and the immune system work hand in hand to regulate ovarian function.

Clinical neurophysiological examination of deafness associated with juvenile motor neurone disease.

Three patients with the syndrome of progressive severe deafness, associated with juvenile onset of motor neurone disease, were examined using conventional audiometry and brainstem auditory evoked response (BAER) recordings, and electrocochleographic recordings were made in two of them. Findings indicate that the deafness had resulted from loss of acoustic nerve fibers and/or sensory cells of the spiral ganglion.

A study of the neurological disorder associated with acute haemorrhagic conjunctivitis due to enterovirus 70.

Ninety cases of the neurological manifestations associated with acute haemorrhagic conjunctivitis caused by Enterovirus 70 (EV 70) are reported. The patients were seen during the widespread epidemics in 1971 and 1981. Male adults were predominantly affected by a "polio-like" paralysis of the limbs and/or cranial nerves. Root pains were often complained of early in the disease. In the absence of a necropsy, clinical and neurophysiological examinations helped to localise the lesions. Significant antibody titres against EV 70 were demonstrated in the serum and more relevantly in the CSF. Though other viruses can cause sporadic and epidemic conjunctivitis and similar paralysis independently, the combination of a haemorrhagic conjunctivitis and a neurological disease mostly simulating poliomyelitis is caused by EV 70 alone. It is therefore suggested that this combination be called "Enterovirus 70 disease". Because of its neurovirulence, it is important to identify this virus at the very beginning of an epidemic of conjunctivitis, so as to limit its spread by strict public health measures.

Polio-like motor paralysis associated with acute hemorrhagic conjunctivitis in an outbreak in 1981 in Bombay, India: clinical and serologic studies.

High and rising neutralizing antibody titers (NATs) to enterovirus type 70 (EV70) were detected in the serum and cerebrospinal fluid (CSF) of patients with polio-like motor paralysis accompanying acute hemorrhagic conjunctivitis (AHC) in an outbreak of AHC in 1981 in Bombay, India. Fifty-four (88.5%) of 61 patients with AHC with or without neurologic disease had serum NATs of greater than or equal to 1:16, and some paired sera from these patients showed significant increases in NAT. Serum from noninfected control subjects had no significant neutralizing antibody to EV70. Thirty-six (94.7%) of 38 CSF specimens from 30 patients with spinal or a combination of spinal and cranial motor paralysis associated with AHC had NATs ranging from 1:2 to 1:256. No neutralizing antibody was found in CSF specimens from patients with AHC alone or in those from non-infected control subjects, and a reduced ratio of serum NAT to CSF NAT was detected in patients with neurologic disease. Therefore, it is highly likely that intrathecal synthesis of antibody occurred in response to direct invasion of the central nervous system by EV70. The results represent strong laboratory evidence of the neurovirulence of EV70.