Thursday, October 22, 2009
Wednesday, October 14, 2009
Verhagen MMM, Abdo WF, Willemsen MAAP. Clinical spectrum of ataxia-telangiectasia in adulthood. Neurology 2009; 73: 430-437 and accompanying editorial.
This important article describes another way adult neurologists cannot completely hide from their brief 3 month training in pediatric neurological diseases that they underwent in training. The summary below focuses on clinical aspects but the article contains genetics information for those interested.
AT is typically an AR childhood disease that one can read about in a 1980 edition of Adams and Victor. Variant AT occurs in older adults as a forme fruste perhaps of the pediatrics form. It is described in about 13 patients. Patients usually had young onset movement disorders, either choreoathetosis or resting tremor. Distal muscle weakness occurred in one patient. By age 27 patients began to experience progressive cerebellar atrophy with eventual development of dysarthria in all, continued movement disorders, nystagmus, dystonias and oculomotor apraxias. EMG/NCS showed either anterior horn cell involvement or sensorimotor polyneuropathy. Cerebellar atrophy on imaging affected vermis primarily.
Minimal telangiectasias of either eye or skin occurred in variant form. Lung function was normal. Four of 13 developed malignancies including ALL, ectopic pituitary tumor, and breast cancer. Alpha feto protein levels were markedly elevated in all patients to ten to fifty times normal, although this is still less than in classic AT. Ig deficiencies occurred in only one patient and were of minor degree.
Adult patients with classic AT also exist and present with cerebellar ataxia, ocular telangiectasia, immunodeficiency, rearrangement of chromosomes 7 and 14, X ray hypersensitivity and elevated alpha feto protein levels. Patients were all wheelchair bound, had growth retardation, endocrinopathy including type 2 DM, diminished secondary sexual characteristics, restrictive lung disease, and more cancer especially lymphoproliferative diseases. Defect is in DNA repair.
Alpha fetoprotein appears to be good screening tool.
Posted by Neurodoc at 6:08 PM
Monday, October 12, 2009
Vanderschueren SW, Mylle M, Dierickx D et al. Monoclonal gammopathy of undetermined significance: significant beyong hematology. Mayo Clin Proc. 2009; 84:842-847.
MGUS is found in 3% of patients older than 50, 5% older than 70, in 7 % of patients seeking medical evaluation, and converts to myeloma at rate of one percent per year. Authors present five OTHER associations of MGUS that are commonly underrecognized.
1. Acquired C1 inhibitor deficiency. should be suspected in patients with repetitive often stereotypic episodes of angioedema, with no urticaria or pruritus or family history, & in pts with recurrent acute abdomen with normal CRP and low C4 levels. Hereditary form occurs in first two decades usually, acquired forms in elderly patients with MGUS in up to 40 % of cases (IgG, IgM or IgA). In acquired forms C1q levels are low due to consumption. Acute prophylaxis can be done with antifibrinolytics eg. transexamic acid or danazol, and acutely FFP has variable success.
2. Systemic capillary leak syndrome should be suspected in patients with repetitive hypovolemic shock, capillary leak and hemoconcentration (in case report, HB went from 15 to 23 in one day). Attacks characterized by prodrome malaise, fatigue, OH, polydipsia, palpebral edema, last 1 to several days and have high fluid requirements during an attack. MGUS usually IgG is typically present. Intestinal edema, ascites, muscular edema, pleural and pericardia effusions occur, may have compartment syndrome. Terbutaline, theophylline, and IVIG are used to treat.
3. Acquired von Willebrand syndrome-- uncommon condition occurs in elderly patietns with no history or family history of bleeding, with MGUS in 50-60 %. Desmopressin works transiently. High dose IVIG has been used. Suspect with mucocutaneous or postop bleeding.
4. Schnitzler syndrome-- heralded by repetitive fevers and chronic, initially nonpruritic urticaria. CRP and ESR are typically very high. MGUS is usually M type. Anakinra, an IL1 antagonist shows promise.
5. Scleromyxedema-- characterized by typical skin eruption and visceral or repetitive neurologic involvement. Case reported of 39 yo man with episodic confusion preceded by flu like illness proceeding to status epilepticus and prolonged postictal coma. Over weeks, appeared erythematous plaques on face and skin creases over glabella , confirmed with biopsy to be scleromyxedema. Tx was plasmapx, IVIG, dexamethasone, autologous stem cell, thalidomide. Its caused by hyaluronic acid deposition in superficial dermis and production of MGUS usually IgA. Also called papular mucinosis and generalized lichen myxedematosus. Occurs in patients usually 30-50 , may include MI as well. Also called dermatoneural syndrome.
Posted by Neurodoc at 6:52 AM