Professor P. K. Thomas: clinician, investigator, editor and leader--a retrospective appreciation.

P. K. Thomas (1926-2008) occupied a prominent place in British and world neurology during the second half of the 20th century. Here, his lasting achievements as clinical neurologist, clinician scientist and experimentalist, editor of monographs and journals and leader of professional developments in the UK and elsewhere are assessed.

Selected contributions to neurology by Philadelphia neurologists since 1980.

On the occasion of the 125th anniversary of the Philadelphia Neurologic Society, 3 short talks were given that highlighted accomplishments by Philadelphia's neurologists over the past 30 years. The theme for the celebration was "Contributions to Neurology by Philadelphia Neurologists, 1980-2008." Each of the 3 speakers was chosen because of his contributions and the sequential time frames in which they occurred. Dr. Arthur K. Asbury detailed the original description of the Lewis-Sumner syndrome, Dr. Michael R. Sperling summarized the growth of epilepsy surgery in Philadelphia, and Dr. Geoffrey K. Aguirre depicted the roots of functional magnetic resonance imaging in Philadelphia.

Overlap of pathology in paralytic rabies and axonal Guillain-Barre syndrome.

We describe clinical and pathological features of a case of paralytic rabies with acute axonal neuropathy that closely resembled axonal Guillain-Barre syndrome. This case emphasizes that there is overlap of both clinical and pathological features in paralytic rabies and axonal Guillain-Barre syndrome. These findings raise the possibility that infectious and autoimmune etiologies can lead to similar morphological changes in the nerves.

Distal symmetrical polyneuropathy: a definition for clinical research. A report of the American Academy of Neurology, the American Association of Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation.

The objective of this report was to develop a case definition of "distal symmetrical polyneuropathy" to standardize and facilitate clinical research and epidemiologic studies. A formalized consensus process was employed to reach agreement after a systematic review and classification of evidence from the literature. The literature indicates that symptoms alone have relatively poor diagnostic accuracy in predicting the presence of polyneuropathy; signs are better predictors of polyneuropathy than symptoms; and single abnormalities on examination are less sensitive than multiple abnormalities in predicting the presence of polyneuropathy. The combination of neuropathic symptoms, signs, and electrodiagnostic findings provides the most accurate diagnosis of distal symmetrical polyneuropathy. A set of case definitions was rank ordered by likelihood of disease. The highest likelihood of polyneuropathy (useful for clinical trials) occurs with a combination of multiple symptoms, multiple signs, and abnormal electrodiagnostic studies. A modest likelihood of polyneuropathy (useful for field or epidemiologic studies) occurs with a combination of multiple symptoms and multiple signs when the results of electrodiagnostic studies are not available. A lower likelihood of polyneuropathy occurs when electrodiagnostic studies and signs are discordant. For research purposes, the best approach to defining distal symmetrical polyneuropathy is a set of case definitions rank ordered by estimated likelihood of disease. The inclusion of this formalized case definition in clinical and epidemiologic research studies will ensure greater consistency of case selection.

Involvement of skeletal muscle in dialysis-associated systemic fibrosis (nephrogenic fibrosing dermopathy).

Nephrogenic fibrosing dermopathy (NFD), a newly recognized scleroderma-like disease, was originally described as a purely cutaneous disorder. More widespread involvement, including fibrosis of pulmonary and cardiac tissues, has been documented only recently, and it has been suggested that a more appropriate designation is dialysis-associated systemic fibrosis. We report five cases of this novel disorder, spanning a spectrum of primarily skin to primarily muscle involvement. Clinical, radiological, electrophysiological, and pathological studies revealed moderate to severe fibrosis of striated muscles. All patients had end-stage renal failure on chronic dialysis, subacute to chronic hardening of the skin and muscles, restriction of limb movements with joint contractures, but normal to only mildly weak muscle strength. Limitation of movements was caused predominantly by skin tightness and induration, and by joint contractures rather than muscle weakness. Computerized tomography showed fibrosis of the fascia and muscles in the most severely affected patients, and electromyography showed mild to severe myopathic changes. Histopathology of affected muscles revealed a spectrum of mild to severe fibrosis, degenerating fibers, and chronic inflammatory cells. These results further support the contention that NFD is not a purely cutaneous disease, but is part of a larger systemic fibrotic process that may involve muscles.

Acute ocular motor mononeuropathies: prospective study of the roles of neuroimaging and clinical assessment.

The role for immediate neuroimaging in patients 50 years of age or older with acute isolated third, fourth, and sixth nerve palsies is controversial. We prospectively evaluated 66 patients, aged 50 years and older (median 67 years, range 50-85), with acute isolated ocular motor mononeuropathies. Our purpose was to evaluate both the role of neuroimaging and the role of clinical assessment in determining etiology. We found that clinical features, including time to maximal diplopic symptoms, were not predictive of etiology (median 2 days to maximal diplopic symptoms for both peripheral microvascular and other etiologies). The presence of any common vascular risk factor, including diabetes mellitus, hypertension, hypercholesterolemia, or coronary artery disease, was significantly associated with peripheral microvascular etiology in this cohort (p=0.0004, Fisher's exact test). Despite the high prevalence of peripheral microvascular ischemia as an etiology in this age group, other causes were identified by magnetic resonance imaging (MRI) or computed tomography (CT) scanning in 14% of patients. Diagnoses included brainstem and skull base neoplasms, brainstem infarcts, aneurysms, demyelinating disease, and pituitary apoplexy. Neuroimaging procedures may have a role in the initial evaluation of patients 50 years of age or older with acute ocular motor mononeuropathies.

Differential distribution of HLA-DQ beta/DR beta epitopes in the two forms of Guillain-Barré syndrome, acute motor axonal neuropathy and acute inflammatory demyelinating polyneuropathy (AIDP): identification of DQ beta epitopes associated with susceptibility to and protection from AIDP.

Guillain-Barré syndrome (GBS), an acute, immune-mediated paralytic disorder affecting the peripheral nervous system, is the most common cause of acute flaccid paralysis in the post-polio era. GBS is classified into several subtypes based on clinical and pathologic criteria, with acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN) being the most common forms observed. To better understand the pathogenesis of GBS and host susceptibility to developing the disease, the distribution of HLA class II Ags along with the seroreactivity to Campylobacter jejuni were investigated in a population of GBS patients from northern China. Using DNA-based typing methods, 47 patients with AMAN, 25 patients with AIDP, and 97 healthy controls were studied for the distribution of class II alleles. We found that the DQ beta RLD(55-57)/ED(70-71) and DR beta E(9)V(11)H(13) epitopes were associated with susceptibility to AIDP (p = 0.009 and p = 0.004, respectively), and the DQ beta RPD(55-57) epitope was associated with protection (p = 0.05) from AIDP. These DQ beta/DR beta positional residues are a part of pockets 4 (DQ beta 70, 71, DR beta 13), 6 (DR beta 11), and 9 (DQ beta 56, 57, DR beta 9); have been demonstrated to be important in peptide binding and T cell recognition; and are associated with other diseases that have a pathoimmunological basis. Class II HLA associations were not identified with AMAN, suggesting a different immunological mechanism of disease induction in the two forms of GBS. These findings provide immunogenetic evidence for differentiating the two disease entities (AMAN and AIDP) and focuses our attention on particular DR beta/DQ beta residues that may be instrumental in understanding the pathophysiology of AIDP.

Co-occurrence of Parkinson's disease with progressive supranuclear palsy.

Parkinson's disease (PD) and progressive supranuclear palsy (PSP) are distinct neurodegenerative disorders. We describe an 81-year-old woman with 3 years of progressive gait unsteadiness, frequent falls, and mild cognitive dysfunction, all considered clinically to be an early fronto-temporal neurodegenerative disorder. She died of an acute myocardial infarction. Examination of her brain revealed alpha-synuclein- and tau-positive inclusions diagnostic of PD and PSP. Immunoelectron microscopy and Western blot analysis confirmed combined PD/PSP. This case provides strategies for the reliable molecular validation of concomitant PD and PSP, and demonstrates the utility of these techniques in patients with atypical clinical presentations.