James O. Donaldson

Neurologic abnormalities in lyme disease without erythema chronicum migrans

The clinical features in eight patients with neurologic abnormalities typical of Lyme disease and elevated titers of antibody to the spirochete, Borrelia burgdorferi, its causative agent, are described. None of the patients had the diagnostic skin lesion, erythema chronicum migrans. Lyme arthritis, the other clinical marker for the disease, developed subsequently in only three. The neurologic abnormalities included aseptic meningitis, encephalitis, cranial neuritis, motor and sensory radiculitis, and myelitis in various combinations. The occurrence of severe encephalitis resulting in dementia in two of these patients and irreversible myelopathy in one enlarges the known spectrum of neurologic abnormalities due to infection with B. burgdorferi. Lyme disease can present with neurologic abnormalities without diagnostic extraneural features, can be suspected on clinical and epidemiologic grounds, and can be diagnosed serologically.

Pathogenesis of pseudotumor cerebri syndromes

Intracrania1 hypertension in the absence of an intracranial mass lesion or hydrocephalus can be caused by an alteration of one or more of the four determinants of cerebrospinal fluid (CSF) pressure: (1) intrasagittal sinus pressure, (2) resistance of arachnoid villi to the egress of CSF, (3) rate of production of CSF, and (4) compliance of the CSF space. The pseudotumor cerebri syndrome of obese young women may be caused partially by increased CSF production. Estrone (produced by the conversion of androstenedione by adipocytes) probably induces the menstrual irregularities of these women and may affect CSF secretion. Pseudotumor cerebri syndromes associated with other conditions may be separated into pathogenic categories.

Invited Review: The Brain in Eclampsia

The occurrence of a convulsion marks the transition of preeclampsia to eclampsia. Although many women who experience eclamptic convulsions recover without neurologic sequelae including epilepsy, the mortality of eclampsia, much due to cerebral lesions, increases with the number of convulsions. A review of the character of the neurological manifestations of toxemia is followed by proposals for their pathogenesis. The author exposes that the neurologic manifestations of eclampsia are those of hypertensive encephalopathy in previously normotensive young women. Hypertensive encephalopathy occurs if sustained mean arterial blood pressure exceeds the upper limit of autoregulation of cerebral perfusion. Thus, the pathophysiological event which compromises the brain is not a convulsion but rather the point at which a preeclamptic womans blood pressure exceeds her upper limit of the autoregulation of cerebral perfusion.A convulsion has been the traditional dividing line between preeclampsia and eclampsia. The dan...

Bacterial lipodipeptide, Lipid 654, is a microbiome-associated biomarker for multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disease of unknown etiology. Infectious agents have been suggested to have a role as environmental factors in MS, but this concept remains controversial. Recently, gastrointestinal commensal bacteria have been implicated in the pathogenesis of autoimmune diseases, but mechanisms underlying the relationship of human systemic autoimmunity with the commensal microbiome have yet to be identified. Consistent with the lack of understanding of pathogenic mechanisms and relevant environmental factors in MS, no blood biomarkers have been identified that distinguish MS patients from healthy individuals. We recently identified a unique gastrointestinal and oral bacteria‐derived lipodipeptide, Lipid 654, which is produced by commensal bacteria and functions as a human and mouse Toll‐like receptor 2 ligand. Using multiple‐reaction‐monitoring mass spectrometry, a critical approach in targeted lipidomics, we now report that Lipid 654 can be recovered in the serum of healthy individuals. Most interestingly, we find that Lipid 654 is expressed at significantly lower levels in the serum of patients with MS compared with both healthy individuals and patients with Alzheimers disease. These results thus identify for the first time a potential mechanism relating the gastrointestinal and oral commensal microbiome to a human systemic autoimmune disease. In addition, these results also identify a potential etiologic environmental factor and novel clinically relevant serum biomarker for MS.

Granulomatous angiitis presenting as chronic meningitis and ventriculitis

A 35-year-old woman had a diffuse encephalopathy with increased intracranial pressure and chronic lymphocytic meningitis. Hypoglycorrhachia and ventricular accumulation of tracer on radionuclide brain scanning suggested an infection. Cerebral cortical and leptomeningeal biopsies were done when she failed to improve with antituberculous therapy, but were not diagnostic. Granulomatous angiitis of the nervous system was diagnosed at postmortem examination and should be considered in the differential diagnosis of culture-negative chronic meningitis.

Cerebrospinal fluid oestrone in pseudotumour cerebri

The concentration of oestrone in the cerebrospinal fluid (CSF) from obese young women with pseudotumour cerebri was much greater than predicted and found in normal subjects. Each woman with pseudotumour cerebri, and a high level of CSF oestrone and a CSF protein less than 0·2 g/l, had clinical improvement when treated with an 800 calorie/day diet and dexamethasone 2 mg/day.

Lymphocyte adherence in multiple sclerosis

It has been reported that peripheral blood lymphocytes from patients with multiple sclerosis (MS) adhere to measles-infected human epithelial cells in significantly greater numbers than do lymphocytes from healthy volunteers or patients with other neurologic diseases. We have confirmed this observation in three separate studies, and have investigated the relationship of lymphocyte adherence to the clinical state. Lymphocyte adherence determination values correlated with the degree of certainty of the clinical diagnosis of MS, and lymphocyte adherence values in individual patients increased during clinical exacerbations. Judicious use of this test may facilitate the diagnosis of MS.

Anosmia and nutritional status

Abstract The present study quantified the food perception, food behavior and possible nutritional risk of anosmic patients. Anosmics were divided into three groups according to the duration of their olfactory symptoms: a) lifelong anosmics (n=9), b) mid-term anosmics (anosmics for five years or more but not lifelong) (n=22), and c) recent-onset anosmics (anosmics for less than five years) (n=22). Patients were compared to controls with no smell problem (n=33). We measured standard anthropometric, biochemical and nutritional parameters (24-hour recall and 3-day food record). Anosmics and controls did not differ in a number of anthropometric measures including body weight and body mass index. Mid-term anosmics showed significantly lower serum albumin levels but not serum total protein. Both recent onset and mid-term anosmics had significantly lower hemoglobin values than the controls but not the lifelong anosmics. A similar pattern was noted with measures of food enjoyment. Nevertheless, the anosmics did not differ in nutrient intake or eat less frequently.

Eclampsia and postpartum cerebral angiopathy

Pre-eclampsia is a protean disease of pregnancy manito garden-variety eclampsia, clinical status and monitoring fested by hypertension, proteinuria and edema. A convulwith transcranial Doppler usually improve over a few days. sion has been the traditional dividing line between the However, cases may have a protracted case which would preeclamptic and eclamptic forms of toxemia of pregnancy be very atypical for eclampsia. A basic difference is that although clinical evidence and neuroimaging indicates that postpartum cerebral angiopathy starts with cerebral inthe brain may be afflicted before a convulsion occurs. volvement whereas the toxemia of pregnancy evolves Although delivery is the ultimate cure, for approximately through the stages of preeclampsia with other organs being 40% the first eclamptic convulsion occurs post partum, affected before the brain. usually within the first 24 hours. Some cases of late It is my opinion that when the pathogenesis of toxemia postpartum eclampsia develop one week or more after a of pregnancy is understood, postpartum cerebral annormal delivery. giopathy will be classified as a subset of that disease. We Evidence is accumulating that the cerebral manimay never be neurological archaeologists enough to refestations of eclampsia are due to hypertensive entrospectively sort out many of the reported case. Case cephalopathy. Angiography has demonstrated smooth segreports of postpartum cerebral angiopathy coincident with mental vasospasm, which is presumably a reflection of the the use of vasoactive substances such as ergonovine, autoregulatory response. This has been demonstrated in bromocriptine and sumatriptan are important observations late postpartum eclampsia. but, I agree with Dr. Zunker and colleagues, that there is A problem is how to classify patients with smooth insufficient evidence to establish a causal relationship. segmental vasospasm in the early puerperium who do not Our knowledge of the brain in eclampsia continues to meet the criteria for pre-eclampsia. Currently this is called evolve from the static study of neuropathology in 1900 to postpartum cerebral angiopathy. Many times this diagnosis dynamic and serial assessments of living patients in 2000. is stumbled upon in the investigation for a suspected Each new technique adds more information from which a cortical venous thrombosis or another entity. The detail of rationale for treatment will develop. The worldwide imporcase reports varies. Some authors may not have understood tance of this disease should not be underestimated. Even in the importance of relative hypertension when compared to the best of hands, the death rate in eclampsia is approxithe patient’s customary blood pressure. Nevertheless many mately 7% with an estimated 50,000 young women dying apparently do not have hypertension or proteinuria. Similar every year worldwide.

Generation of phenotypic helper/inducer and suppressor/ cytotoxic T-cell lines from cerebrospinal fluid in multiple sclerosis

The investigation of cell-mediated events in man has been largely limited to the study of the cells in the peripheral circulation. The study of T cells from localized anatomic compartments has been difficult due to the small numbers of cells usually obtainable from these sites. Investigation of such compartmentalized responses theoretically may yield information relating to both normal immunoregulation and autoimmune diseases--information that may not be obtainable through the investigation of the circulating cellular immune system. Utilizing cerebrospinal fluid (CSF) lymphocytes from patients with multiple sclerosis as a model of compartmentalized immunologically relevant cells, the technology for the generation of long-term T-cell lines from compartments both in continuous culture and after cryopreservation and that consist of both helper/inducer and suppressor/cytotoxic phenotypes have been generated. The 10(4) to 10(5) CSF cells obtained initially from individual patients have often been expanded into greater than 10(8) total cells within 4 months. The ability to generate large, stable, cryopreservable helper and suppressor/cytotoxic T-cell lines from limited access compartments will allow for new investigative approaches into both normal immunoregulation and autoimmune diseases in man.