Spasmodic dysphonia is a neurological disorder characterized by involuntary spasms in the laryngeal muscles during speech production. Although the clinical symptoms are well characterized, the pathophysiology of this voice disorder is unknown. We describe here, for the first time to our knowledge, disorder-specific brain abnormalities in these patients as determined by a combined approach of diffusion tensor imaging (DTI) and postmortem histopathology. We used DTI to identify brain changes and to target those brain regions for neuropathological examination. DTI showed right-sided decrease of fractional anisotropy in the genu of the internal capsule and bilateral increase of overall water diffusivity in the white matter along the corticobulbar/corticospinal tract in 20 spasmodic dysphonia patients compared to 20 healthy subjects. In addition, water diffusivity was bilaterally increased in the lentiform nucleus, ventral thalamus and cerebellar white and grey matter in the patients. These brain changes were substantiated with focal histopathological abnormalities presented as a loss of axonal density and myelin content in the right genu of the internal capsule and clusters of mineral depositions, containing calcium, phosphorus and iron, in the parenchyma and vessel walls of the posterior limb of the internal capsule, putamen, globus pallidus and cerebellum in the postmortem brain tissue from one patient compared to three controls. The specificity of these brain abnormalities is confirmed by their localization, limited only to the corticobulbar/corticospinal tract and its main input/output structures. We also found positive correlation between the diffusivity changes and clinical symptoms of spasmodic dysphonia (r = 0.509, P = 0.037). These brain abnormalities may alter the central control of voluntary voice production and, therefore, may underlie the pathophysiology of this disorder.
BackgroundMorgellons is a poorly characterized constellation of symptoms, with the primary manifestations involving the skin. We conducted an investigation of this unexplained dermopathy to characterize the clinical and epidemiologic features and explore potential etiologies.MethodsA descriptive study was conducted among persons at least 13 years of age and enrolled in Kaiser Permanente Northern California (KPNC) during 2006–2008. A case was defined as the self-reported emergence of fibers or materials from the skin accompanied by skin lesions and/or disturbing skin sensations. We collected detailed epidemiologic data, performed clinical evaluations and geospatial analyses and analyzed materials collected from participants' skin.ResultsWe identified 115 case-patients. The prevalence was 3.65 (95% CI = 2.98, 4.40) cases per 100,000 enrollees. There was no clustering of cases within the 13-county KPNC catchment area (p = .113). Case-patients had a median age of 52 years (range: 17–93) and were primarily female (77%) and Caucasian (77%). Multi-system complaints were common; 70% reported chronic fatigue and 54% rated their overall health as fair or poor with mean Physical Component Scores and Mental Component Scores of 36.63 (SD = 12.9) and 35.45 (SD = 12.89), respectively. Cognitive deficits were detected in 59% of case-patients and 63% had evidence of clinically significant somatic complaints; 50% had drugs detected in hair samples and 78% reported exposure to solvents. Solar elastosis was the most common histopathologic abnormality (51% of biopsies); skin lesions were most consistent with arthropod bites or chronic excoriations. No parasites or mycobacteria were detected. Most materials collected from participants' skin were composed of cellulose, likely of cotton origin.ConclusionsThis unexplained dermopathy was rare among this population of Northern California residents, but associated with significantly reduced health-related quality of life. No common underlying medical condition or infectious source was identified, similar to more commonly recognized conditions such as delusional infestation.
The histomorphologic characteristics and chemical composition of the crystals associated with suspected pet food-induced nephrotoxicosis in 3 dogs are described. Kidney specimens from 2 dogs, a 3-year-old Parson Russell Terrier and a 3-year-old Bernese Mountain Dog, were examined. Both developed acute renal failure after eating canned pet food on the 2007 Menu Foods recall list. The third case was a kidney specimen from a 1-year-old mixed-breed dog from a similar 2004 outbreak of canine renal failure in Taiwan, which occurred after eating a commercial dog food. Hematoxylin and eosin (HE), 72-hour Oil Red O (ORO72h), Alizarin Red S (pH 4.1-4.3), and Von Kossa stains; infrared (IR) spectroscopy; and scanning electron microscopy with energy dispersive X-ray analysis (SEM/EDXA) were performed to determine the histomorphologic characteristics and chemical composition of the crystals observed in each case. Histomorphologic findings in each case included acute, marked tubular degeneration and necrosis with many intratubular birefringent crystals, and lymphoplasmacytic interstitial nephritis. In each case, most of the crystals were rough, pale brown, and stained with ORO72h but did not stain with Alizarin Red S (pH 4.1-4.3) or Von Kossa stains; these features were consistent with a plastic or lipid. IR spectroscopy and SEM/EDXA results were consistent with melamine-containing crystals. A second crystal type identified in each case was smooth and platelike with staining characteristics and IR spectroscopy and SEM/EDXA results consistent with calcium oxalate crystals. Melamine-containing crystals have distinct light microscopic, histochemical, and SEM/EDXA characteristics that facilitate their identification in tissue.
Crospovidone is an insoluble polymer of N-vinyl-2-pyrrolidone that is used as a disintegrant in pharmaceutical tablets. It can potentially embolize to the lung when aqueous tablet suspensions are injected intravenously. In this report, we identified embolized crospovidone in autopsy-derived lung tissue from three adult IV drug users, 1 man and 2 women, whose ages respectively were 27, 38, and 40 years. Suspected crospovidone was compared with pharmaceutical-grade crospovidone by means of histochemical stains, transmission electron microscopy, and infrared spectroscopy. Similar particles were also observed by light microscopy in a 4-mg tablet of hydromorphone, a preparation prescribed to two of the patients. Two patients had sickle cell disease and were taking methadone and/or hydromorphone for pain management; the third was receiving parenteral hyperalimentation after small bowel resection. Crospovidone appeared as deeply basophilic, coral-like particles within pulmonary arteries and in extravascular foreign-body granulomas. Intrapulmonary crospovidone stained similarly to the pure substance, including intense staining with mucicarmine, Congo red, and Masson trichrome. With Movat pentachrome stain, both intravascular and purified crospovidone appeared orange-yellow, whereas most interstitial particles associated with giant cells stained blue-green. Alcian blue failed to stain intravascular or purified crospovidone but strongly decorated some phagocytized particles. Ultrastructurally, both purified powder and tissue deposits of crospovidone appeared as irregular, electron dense, laminated, and finely granular material. Intrapulmonary crospovidone was associated with inflammatory cells and exhibited degenerative changes. By infrared spectroscopy, crospovidone in tissue had the same spectral characteristics as pharmaceutical grade crospovidone and the library reference, polyvinylpyrrolidone (PVP). We conclude that crospovidone contributes to pulmonary vascular injury in some persons who illicitly inject pharmaceutical tablets. It is readily identifiable histologically and distinguishable from other tablet constituents, such as cornstarch, talc, and microcrystalline cellulose. Pharmaceutical tablets typically consist of active ingredients and a variety of insoluble filler substances, such as talc, microcrystalline cellulose, and cornstarch, which provide bulk and impart physical properties to tablet preparations (1). Pulmonary foreign body granulomatosis caused by the embolization of these filler materials occurs when aqueous suspensions of tablets intended for oral consumption are injected intravenously (1-3). Some of the agents used in this manner, either alone or in combination, include methadone hydrochloride, tripelennamine hydrochloride (Pyribenzamine), methylphenidate (Ritalin), and pentazocine (Talwin; 3-6). Pulmonary angiothrombotic granulomatosis caused by talc, cornstarch and/or microcrys-
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