Objective: To improve clinical recognition and provide research diagnostic criteria for three clinical syndromes associated with frontotemporal lobar degeneration. Methods: Consensus criteria for the three prototypic syndromes-frontotemporal dementia, progressive nonfluent aphasia, and semantic dementia-were developed by members of an international workshop on frontotemporal lobar degeneration. These criteria build on earlier published clinical diagnostic guidelines for frontotemporal dementia produced by some of the workshop members. Results: The consensus criteria specify core and supportive features for each of the three prototypic clinical syndromes and provide broad inclusion and exclusion criteria for the generic entity of frontotemporal lobar degeneration. The criteria are presented in lists, and operational definitions for features are provided in the text. Conclusions: The criteria ought to provide the foundation for research work into the neuropsychology, neuropathology, genetics, molecular biology, and epidemiology of these important clinical disorders that account for a substantial proportion of cases of primary degenerative dementia occurring before the age of 65 years.

Frontotemporal lobar degeneration A consensus on clinical diagnostic criteria

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(05)71142-9.pdf

Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders.

The hygiene hypothesis postulates that an environment with a high incidence of infectious diseases protects against allergic and autoimmune diseases, whereas hygienic surroundings increase the incidence of these disorders This review examines the evidence in support of the hygiene hypothesis and offers a number of mechanisms that could explain the relation between sanitary conditions and susceptibility to allergic and autoimmune diseases

https://www.nejm.org/doi/pdf/10.1056/NEJMra020100

The Effect of Infections on Susceptibility to Autoimmune and Allergic Diseases

Degeneration and regeneration of the nervous system

OBJECTIVE\nTo develop a standardized nomenclature system for the neuropsychiatric syndromes of systemic lupus erythematosus (NPSLE).\n\n\nMETHODS\nAn international, multidisciplinary committee representing rheumatology, neurology, psychiatry, neuropsychology, and hematology developed case definitions, reporting standards, and diagnostic testing recommendations. Before and after the meeting, clinician committee members assigned diagnoses to sets of vignettes randomly generated from a pool of 108 NPSLE patients. To assess whether the nomenclature system improved diagnostic agreement, a consensus index was developed and pre- and postmeeting scores were compared by t-tests.\n\n\nRESULTS\nCase definitions including diagnostic criteria, important exclusions, and methods of ascertainment were developed for 19 NPSLE syndromes. Recommendations for standard reporting requirements, minimum laboratory evaluation, and imaging techniques were formulated. A short neuropsychological test battery for the diagnosis of cognitive deficits was proposed. In the postmeeting exercise, a statistically significant improvement in diagnostic agreement was observed.\n\n\nCONCLUSION\nThe American College of Rheumatology (ACR) Nomenclature for NPSLE provides case definitions for 19 neuropsychiatric syndromes seen in SLE, with reporting standards and recommendations for laboratory and imaging tests. It is intended to facilitate and enhance clinical research, particularly multicenter studies, and reporting. In clinical settings, consultation with other specialists may be required. It should be useful for didactic purposes but should not be used uncritically or as a substitute for a clinical diagnosis. The complete case definitions are available on the ACR World Wide Web site: http://www.rheumatology .org/ar/ar.html.

The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes

Ninety-two patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have been studied in order to define better the clinical features, course and prognosis of the condition and to identify possible aetiological factors. Sural nerve biopsy was performed on 87 subjects. Electrophysiological studies were undertaken on all patients and demonstrated marked slowing of motor conduction and impairment of sensory conduction. The onset was usually gradual but there was a rapid rate of onset in 15 (16%) patients. Males were more commonly affected than females. Weakness and paraesthesiae were the most common symptoms but pain was frequently a feature. Age of onset ranged from 2 to 72 years. Sixty patients (65%) had a relapsing course and 32 patients (35%) a progressive or monophasic course; there was a significantly earlier age of onset in patients with relapsing disease. Thirty-two patients (35%) gave a history of preceding infection or some other possible antecedent precipitating event and there was a significantly higher titre for cytomegalovirus antibodies in the serum of patients with CIDP than in controls. The patients were followed up for an average time of approximately ten years. Most patients (73%) had made a good recovery and were independent, but 7 patients had either died or were completely immobilized as a result of their disease. The value of treatment with corticosteroid therapy, immunosuppressive agents and plasma exchange is discussed.

Chronic inflammatory demyelinating polyradiculoneuropathy. A clinical and electrophysiological study of 92 cases.

Tests of autonomic function were performed on 16 subjects with diabetic neuropathy. Abnormal sweating occurred in 10/10 (100 per cent), postural hypotension in 7/16 (44 per cent), an abnormal Valsalva ratio in 7/11 (64 per cent), and denervation hypersensitivity to phenylephrine in 2/8 (25 per cent) of patients tested. A quantitative assessment of baroreceptor function was made. In diabetics, there was a reduced resting heart period, heart period range and mean gain. Quantitative histological studies were performed on the greater splanchnic nerves removed at autopsy from 9 control subjects and from 8 subjects with diabetic neuropathy. The fibre density was significantly reduced in the greater splanchnic nerve of diabetics. The predominant pathology on teased fibre preparations was that of demyelination. Disordered blood pressure control in diabetes correlated with the pathological abnormalities in the sympathetic nervous system. Light and electronmicroscopic studies were performed on the sural nerves of 2 diabetic subjects with autonomic dysfunction. The predominant change was active axonal degeneration affecting mainly unmyelinated and small myelinated fibres.

The sympathetic nervous system in diabetic neuropathy. A clinical and pathological study.

The prevalence of multiple sclerosis in the Australian-born population in five different regions of Australia has a strong correlation with latitude, the disease becoming increasingly prevalent with increasing south latitude. In this study, the prevalence in the migrant population from the UK and Ireland (UKI) in the different regions also showed a significant correlation with latitude, but this relationship was strongly influenced by the high prevalence in Hobart. Except for Hobart, the prevalence in migrants was considerably less than that in their countries of origin. The prevalence of multiple sclerosis among those migrating before the age of 15 years from the high-risk UKI to lower-risk Australia was not significantly different to that among those migrating at or after that age, and this finding was confirmed in a case-control study which demonstrated little association between age at migration and risk of developing multiple sclerosis. These findings suggest that the risk from environmental factors in multiple sclerosis may operate over a period of many years and not only in childhood and early adult life.

/pdf/the-age-range-of-risk-of-developing-multiple-sclerosis-1410nsidi5.pdf

The age-range of risk of developing multiple sclerosis: evidence from a migrant population in Australia.

An epidemiological survey of multiple sclerosis (MS) in three Australian cities, Perth, Newcastle and Hobart, was undertaken with its prevalence day being the national census day on June 30, 1981, exactly twenty years after a previous survey of the same cities. The relationship between increasing prevalence and increasing south latitude found in the 1961 survey was confirmed in this present study. Prevalence rates had increased significantly over the twenty years between the studies. Over the same time period incidence rates had also increased in Newcastle and Hobart but had remained essentially stable in Perth although these changes were not significant. The rise in prevalence was due to a combination of factors of differing importance in each city. These factors included better case ascertainment, increased recognition of the less severely disabled patient, increased survival time and differential immigration of a population at a higher risk of developing MS than the indigenous population. Finally, analysis of MS prevalence rates amongst migrant populations in Perth and Hobart suggested that either the risk of acquisition of MS may extend over a wider age range than is generally accepted or that environmental factors prevalent in the former city have modified disease expression there.

The epidemiology of multiple sclerosis in three australian cities: perth, newcastle and hobart

Hereditary neuropathy with liability to pressure palsies (HNPP) has been a associated with a deletion of 1.5 megabases of chromosome 17p. One of four biopsy proven HNPP families that we have studied did not possess this deletion. As the deleted DNA region includes the coding region for a peripheral myelin gene (PMP22), we used single strand conformation analysis to examine this gene for mutations in the non-deleted HNPP family. An abnormal fragment in exon 1 was identified, and sequencing revealed a two base pair deletion in all affected family members. The deletion results in a frame shift, providing strong evidence that this gene has an important role in the pathogenesis of the disease.

James G. McLeod

Papers

Chronic inflammatory demyelinating polyradiculoneuropathy. A clinical and electrophysiological study of 92 cases.

The sympathetic nervous system in diabetic neuropathy. A clinical and pathological study.

The age-range of risk of developing multiple sclerosis: evidence from a migrant population in Australia.

The epidemiology of multiple sclerosis in three australian cities: perth, newcastle and hobart

A frame shift mutation in the PMP22 gene in hereditary neuropathy with liability to pressure palsies.