Roberta J. Seidman

L-tryptophan-associated eosinophilic perimyositis, neuritis, and fasciitis. A clinicopathologic and laboratory study of 25 patients.

We have described the spectrum and prevalence of the clinical and laboratory manifestations of a multisystem disorder associated with the ingestion of L-tryptophan. At least 3 subsets of clinical disease have been identified: 1) a neuromuscular disorder which may present with myalgias and mild weakness and then progress to quadriparesis related to an axonal neuropathy and interstitial myositis (perimyositis), 2) a syndrome of eosinophilic fasciitis with characteristic cutaneous induration, and 3) the Löffler syndrome consisting of pulmonary infiltrates with eosinophilia. Corticosteroids may be useful for patients with the Löffler syndrome and offer only a modest benefit in the majority of patients with neuromuscular disease. The clinical course appears to be chronic, and the long-term sequelae of this disorder are unknown. The etiologic agent remains undetermined; however, studies are in progress to examine the mechanism of eosinophilia, appropriate therapeutic intervention, and the long-term outcome of the affected individuals.

Head trauma can initiate the onset of adreno-leukodystrophy.

X-linked adreno-leukodystrophy and its adult variant, adrenomyeloneuropathy, are caused by mutations in ABCD1 that encodes a peroxisomal membrane protein of unknown physiological significance. In spite of identical mutations, they can have markedly divergent neurological and neuropathologic characteristics. Adreno-leukodystrophy classically presents in normal boys with mild neuropsychiatric features, which progress to frank neurological signs, the vegetative state and death in approximately three years. Adrenomyeloneuropathy typically affects young men with spastic paraparesis and sensory ataxia that can progress over decades. The neuropathologic correlate for adreno-leukodystrophy is severe inflammatory demyelination of posterior cerebral white matter, while a chronic distal axonopathy of spinal cord and peripheral nerve occurs in adrenomyeloneuropathy. Consequently, both modifier genes and environmental factors have been implicated in their pathogeneses. We report five cases of adreno-leukodystrophy whose onsets were initiated by moderate to severe head trauma, two of whom were conversions from adrenomyeloneuropathy. Their clinical courses were rapidly incapacitating, short (i.e., weeks to a few years) and fatal due to marked cerebral inflammatory demyelination. These cases, in concert with several previous reports, indicate that head trauma is one environmental factor that can have a profoundly deleterious effect on those genetically at risk for, or with milder clinical phenotypes of, this disease. Avoidance of potential head trauma and a rapid response to episodes of moderate to severe head trauma in this patient population seem prudent.

Cutaneous manifestations of the L-tryptophan-associated eosinophilia-myalgia syndrome: a spectrum of sclerodermatous skin disease.

The natural history of the clinical and pathologic features of skin disease was reviewed prospectively in 30 patients with the L-tryptophan-associated eosinophilia-myalgia syndrome. Overall, cutaneous manifestations developed in 26 patients (87%). Early lesions were nonspecific and characterized predominantly by an erythematous macular eruption on the trunk and extremities. The most characteristic abnormality noted was the spectrum of sclerodermatous disease in 15 patients (50%) often after a subacute stage of peripheral or truncal edema. Clinical and/or biopsy evidence of eosinophilic fasciitis was seen in nine patients (30%). Findings consistent with diffuse, limited, or localized scleroderma were subsequently observed in nine patients (33%). Small mucinous papules, similar to those seen in scleromyxedema, were found in five patients (17%). Alopecia, frequently a late sequela, developed in 11 (37%). Common histologic features included papillary dermal fibrosis, dermal and fascial infiltrates consisting of mononuclear cells and eosinophils, deposition of glycosaminoglycans in the dermis, and, in some patients, numerous mast cells.

Glial transforming growth factor (TGF)-β isotypes in multiple sclerosis: differential glial expression of TGF-β1, 2 and 3 isotypes in multiple sclerosis

Abstract We studied glial transforming growth factor (TGF)-β isotype expression in 14 cases of multiple sclerosis. Acute active lesions exhibited selective TGF-β2 immunoreactivity of lesion encircling ramified microglia. In contrast, astrocytes within chronic active white matter lesions expressed all three isotypes. Chronic active lesions which extended into cortex exhibited selective cortical astrocyte TGF-β2 expression. This isotype was also selectively expressed by astrocytes in apparently normal white matter. A similar pattern of glial TGF-β expression was seen in the pathological control, progressive multifocal leukoencephalopathy. The results suggest that TGF-β cytokines are locally expressed in demyelination and that the β2 isotype may be uniquely regulated.

The Neuromuscular Pathology of the Eosinophilia-Myalgia Syndrome

The Eosinophilia-Myalgia Syndrome (EMS) is a recently recognized disorder in patients ingesting pharmacologic doses of L-tryptophan. We studied the lesions of skeletal muscle, peripheral nerve and skin in 12 cases of EMS. Perimyositis was severe in four, moderate in two, mild in three and absent in three cases. The lesions contained many eosinophils, T-helper cells, mast cells and activated macrophages. Type 2 myofiber atrophy was present in five cases and in one, this was the only pathologic finding. Severe epineurial inflammation was seen in the three sural nerve biopsies. Indirect evidence for peripheral neurologic involvement in three other cases consisted of inflammation surrounding intramuscular nerve twigs (two cases) and neurogenic atrophy (one case). Phlebitis accompanied the connective tissue inflammation in five cases and endarteritis in one. Fasciitis was present in three of four skin biopsies and dermal fibrosis in one.

Paraganglioma of the cauda equina: Case report with magnetic resonance imaging description

The case of a 35-year-old white man with a cauda equina syndrome is presented. Magnetic resonance imaging confirmed the diagnosis, and radiation treatment successfully treated the condition.

Automatic histopathology image analysis with CNNs

We define Pathomics as the process of high throughput generation, interrogation, and mining of quantitative features from high-resolution histopathology tissue images. Analysis and mining of large volumes of imaging features has great potential to enhance our understanding of tumors. The basic Pathomics workflow consists of several steps: segmentation of tissue images to delineate the boundaries of nuclei, cells, and other structures; computation of size, shape, intensity, and texture features for each segmented object; classification of images and patients based on imaging features; and correlation of classification results with genomic signatures and clinical outcome. Executing a Pathomics workflow on a dataset of thousands of very high resolution (gigapixels) and heterogeneous histopathology images is a computationally challenging problem. In this paper, we use Convolutional Neural Networks (CNN) for automatic recognition of nuclear morphological attributes in histopathology images of glioma, the most common malignant brain tumor. We constructed a comprehensive multi-label dataset of glioma nuclei and applied two CNN based methods on this dataset. Both methods perform well recognizing some but not all morphological attributes and are complementary with each other.

Ectopic craniopharyngioma of the fourth ventricle in a patient with Gardner syndrome.

Ectopic craniopharyngioma is uncommon and a craniopharyngioma confined purely within the fourth ventricle is extremely rare. We report a craniopharyngioma of the fourth ventricle in a 20-year-old man with Gardner syndrome. Imaging characteristics of craniopharyngiomas and fourth ventricle lesions are discussed with a review of the literature regarding the pathogenesis of craniopharyngiomas and the possible association with Gardner syndrome.

Ischemic and Hemorrhagic Strokes due to Eosinophilic Granulomatosis with Polyangiitis.

BACKGROUND We report a case of ischemic and hemorrhagic strokes occurring almost simultaneously in a patient diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA) previously known as Churg-Strauss vasculitis. To our knowledge, this is the first known case. METHODS A 59-year-old man presented with a 2-month history of bilateral leg weakness, difficulty ambulating, and dyesthesias. While in the hospital, he developed acute right hand weakness, and magnetic resonance imaging of the brain revealed multiple, bilateral ischemic infarcts. After a few days, he acutely became unresponsive and was found to have a large left frontal hematoma and underwent emergent hematoma evacuation. His weakness was unexplained by the infarcts based on location and so a peripheral process was suspected. RESULTS Nerve conduction studies showed severe axonal sensorimotor neuropathy. A sural nerve biopsy showed necrotizing vasculitis, consistent with EGPA. CONCLUSIONS EGPA is the rarest of the antineutrophilic cytoplasmic antibody vasculitides. The peripheral nervous system is frequently involved, but the central nervous system can also be affected. The vasculitis damages the vessel walls, which leads either to stenosis or to dilatation, resulting in ischemic or bleeding consequences which can occur simultaneously, such as in this case. Caution should be exercised when prescribing antiplatelet therapy to such patients.

Intraspinal psammomatous melanotic schwannoma not associated with Carney complex: case report

The authors present a case of intraspinal malignant psammomatous melanotic schwannoma (PMS) not associated with Carney complex and review all reported cases not associated with this syndrome. The focus of this review paper is on the characteristics of the malignant progression of PMS. A 54-year-old man had a history of squamous cell carcinoma of the neck and tonsillar carcinoma. The patients serial CT scanning study showed a mass in the left C-5 foramen. On presentation he was neurologically intact. After 18 months, the patient developed radiating pain down the left arm with decreased sensation. MRI of the cervical spine showed an enhancing 2.1 × 1.5 × 1.9-cm mass in the left C5-6 foramen. A C5-6 hemilaminectomy was performed with gross-total removal of the tumor. At 3 months postoperatively, the patient developed new-onset pain and weakness. MRI showed a dumbbell-shaped mass in the left C-7 foramen. MRI of the pelvis showed a 1.4 × 1.0-cm lesion on the right ischium and a 1.1 × 2.8-cm lesion on the right inferior pubic ramus. Anterior cervical discectomy of C5-6 and C6-7 with corpectomy of C-6 with subtotal resection of the tumor was completed. PMS should not be considered a benign tumor because in 41.1% of patients, including the patient in this report, the tumor progresses to malignancy. Long-term follow-up is needed in these patients. New surgical treatment plans should be considered.