Noninvasive evaluation of adult onset myopathy from carnitine palmitoyl transferase II deficiency using proton magnetic resonance spectroscopy.

OBJECTIVE: The adult onset metabolic myopathy of carnitine palmitoyl transferase II (CPT II) deficiency is under-recognized, in part due to variable degrees of enzyme deficiency and symptomatology, as well as limitations in means for noninvasive evaluation. We describe a proton magnetic resonance spectroscopy (MRS) technique, using a standard clinical magnetic resonance imaging scanner, to diagnose and help monitor the response to therapy in adult CPT II deficiency. METHODS: A 53-year-old woman presented with a long standing history of diffuse aching and fatigue provoked by high fat intake, fasting, or prolonged exertion. Muscle biopsy revealed myopathic features and a deficiency (33% of control) of CPT II activity with elevated palmitoyl carnitine. Proton MRS of the soleus muscle was performed using a 1.5 Tesla scanner before and during dietary therapy. RESULTS: Proton MRS revealed shortening of the transverse relaxation time (T2), consistent with increased acetylation of the carnitine pool. The symptoms resolved completely by treatment with frequent feedings of a high carbohydrate diet low in long chain fatty acids supplemented with medium chain triglycerides and L-carnitine. Recovery of normal muscle MRS and carnitine T2 relaxation was documented by the third month of therapy. CONCLUSION: Proton MRS is a novel, potentially useful, and readily available adjunct in the diagnosis and therapeutic monitoring of muscle CPT II deficiency.

Case of the month: March 1999--A 26 year old HIV positive male with dura based masses.

A 26-year-old male with AIDS presented with a chief complaint of headaches and neck pain. An MRI revealed two enhancing extra-axial dura based masses, one in the area of the left sphenoid wing and one at the level of C2-3. In both cases, microscopic sections showed actin positive spindle cell neoplasms with long slender nuclei, consistent with leiomyomas. Both tumors were positive for Epstein Barr virus by in situ hybridization. This case report serves to emphasize the importance of considering soft tissue tumors such as leiomyoma in the differential diagnosis of mass lesions that occur in the central nervous system in AIDS and discusses the role of EBV in tumorigenesis.

Abnormalities in central nervous system development in osteogenesis imperfecta type II.

Osteogenesis imperfecta (OI) type II is a perinatally lethal condition resulting from mutations in type I collagen genes. In addition to characteristic skeletal anomalies, OI type II has recently been shown to be associated with neuropathological alterations, specifically perivenous microcalcifications, and impaired neuroblast migration. In light of these findings, and because type I collagen promotes neuritic maturation both in vitro and in vivo, we sought to determine if additional central nervous system (CNS) developmental anomalies could be found in previously autopsied OI type II cases, and if specific abnormalities correlate with OI subtypes. We retrospectively studied brains of nine patients diagnosed with OI. Of these, seven were OI type II: five were OI type IIA, one was type IIB, and one was type IIC. One OI type I specimen and one OI type III brain were included for comparison, as well as five controls. The IIC brain showed hippocampal malrotation, agyria, abnormal neuronal lamination, diffuse hemorrhage, and periventricular leukomalacia (PVL). The IIB brain had white matter gliosis, PVL, and perivascular calcifications, but was normally developed. Of the five type IIA brains, two showed migrational defects with coexisting PVL and gliosis, two were normally developed with similar white matter injuries, and one was grossly normal. These findings support the contention that collagen mutations might negatively impact CNS development.

Mitochondrial DNA polymerase gamma deficiency and mtDNA depletion in a child with Alpers' syndrome.

Deficiency of mitochondrial DNA polymerase gamma activity was found in a patient with mtDNA depletion and Alpers' syndrome. Metabolic evaluation revealed fasting hypoglycemia, dicarboxylic aciduria, and reduced activity of the electron transport chain in skeletal muscle. The patient died in early childhood of fulminant hepatic failure, refractory epilepsy, lactic acidemia, and coma. mtDNA content was 30% of normal in skeletal muscle and 25% in the liver. The activity of mtDNA polymerase gamma was undetectable.

Clinical implications of clubfoot histopathology.

Ipsilateral peroneus brevis muscle histopathology was studied in 64 children with idiopathic rigid equinovarus at the setting of initial posteromedial-lateral release. Fifty percent of biopsies demonstrated abnormal muscle fiber morphology, classified as congenital fiber-type disproportion or fiber-size variation. Forty-one infants (59 feet) underwent initial surgical intervention within the first year of life with a minimum 2-year follow-up. Feet with abnormal muscle histology had a significantly greater incidence of recurrent equinovarus deformity requiring reoperation; the relative risk of clubfoot recurrence in children with fiber abnormalities was 5.6. Male patients with bilateral deformity and abnormal peroneus brevis histology had a particularly high incidence of recurrent equinovarus. Developmental internal tibial torsion requiring surgical intervention was also greater in the abnormal-fiber histology group. The incidence of postoperative metatarsus adductus/varus necessitating surgery was comparable despite histologic findings. Thus muscle-fiber abnormalities are prevalent in idiopathic equinovarus. Such fiber-type anomalies may predict recurrent limb deformities.

Case of the month: January 1998--43 year old male with radicular pain.

A 43-year-old male presented with progressively worsening right lower extremity pain. MRI of the spine showed a discrete intradural, extramedullary, homogeneously enhancing, sausage-shaped mass at L1-L2, noted intraoperatively to expand the filum terminale. Gross, histological, and electron microscopic findings were those of a paraganglioma. The case is used to discuss the differential diagnosis for sausage-shaped tumors of the filum terminale.

Amebic meningoencephalitis caused by Balamuthia mandrillaris: case report and review.

Balamuthia mandrillaris, formerly referred to as a leptomyxid ameba, is a free-living ameba that has recently been identified as a cause of meningoencephalitis. Previously, only two genera, Naegleria and Acanthamoeba, were recognized as causes of central nervous system (CNS) infections in humans. In contrast to Naegleria, Balamuthia causes a subacute-to-chronic infection of the CNS. Distinct from Acanthamoeba, which appears to favor the immunocompromised host, Balamuthia is capable of infecting both healthy and immunosuppressed hosts. Retrospective analyses as well as an accumulation of newly identified cases have demonstrated that this ameba is an increasingly important pathogen to recognize. We report the isolation, histopathologic features, and confirmation by indirect immunofluorescence of B. mandrillaris in a case of fatal amebic meningoencephalitis.