Magnetic resonance spectroscopy in the evaluation of treatment efficacy in unipolar major depressive disorder: a review of the literature.

More and more neuroimaging studies are using in vivo proton magnetic resonance spectroscopy (1H-MRS) to explore correlates of response to therapy in major depressive disorder (MDD). Their aim is to further understanding of the effects of neurotransmitter changes in areas involved in MDD and the mechanisms underlying a good treatment response. We set out to summarise the literature from the past fifteen years on biochemical correlates of treatment response in MDD patients, reflected in pre- and post-therapy changes in 1H-MRS measurements. Our literature search identified fifteen articles reporting 1H-MRS studies in MDD treatment; no study used 1P-MRS. Despite the wide diversity of 1H-MRS methods applied, brain regions studied, and metabolite changes found, there emerged strong evidence of a correlation between changes in neurometabolite concentrations, in particular glutamate, N-acetylaspartate and choline, and a good treatment response to pharmacotherapy or antidepressant stimulation techniques.

Can genes influencing muscle function affect the therapeutic response to enzyme replacement therapy (ERT) in late-onset type II glycogenosis?

The purpose of this study is to analyze the role of genes known to influence muscle performances on the outcome after enzyme replacement treatment (ERT) in type II Glycogenosis (GSDII). We analyzed 16 patients receiving ERT for ≥two years. We assessed the changes in muscle strength by hand-held dynamometry, muscle mass by quantitative MRI, and resistance to exercise by the 6-minute walking test. Exercise gene assessment included angiotensin converting enzyme insertion/deletion polymorphism (ACE), alpha-actinin3 R577X polymorphism (ACTN3), and peroxisome proliferator activated receptor alpha G/C polymorphism (PPARα). Independent of disease severity, one third of patients had a poor response to ERT, which was found to be associated with ACE DD genotype. The ACTN3 null polymorphism appeared to exert a positive effect on treatment efficacy, while PPARα did not seem to exert any influence at all. We conclude that poor treatment outcome in ACE DD genotypes is in line with previous observation of a worse disease course in this subpopulation, and suggests the need for a more careful follow-up and individualized treatment approaches for these patients. Exercise genes may provide a new opportunity for studying the outcome after treatment and the muscle regeneration abilities in other models of genetic myopathies.

Changes in skeletal muscle qualities during enzyme replacement therapy in late-onset type II glycogenosis: temporal and spatial pattern of mass vs. strength response.

Muscle quality is defined as muscle strength generated per unit muscle mass. If enzyme replacement therapy (ERT) has some effects on type II glycogenosis (GSDII) skeletal muscle pathology, we should be able to measure a change in strength and mass. We conducted a prospective study including 11 patients aged 54.2 ± 11.2 years, referring to a single institution and receiving ERT for ≥2 years. Median Walton score was 3 (2.5-6). Lower limb skeletal muscles were assessed by dynamometry and quantitative muscle MRI. Three segments (anterior thigh, posterior thigh, leg) were analysed separately. Clinical-MRI correlations were searched for at T0, T6/T8, and T18/24. Changes in lean and fat body composition were assessed by bioelectrical impedance analysis. We found that the anterior thigh showed the best therapeutic response, with an improvement in muscle quality (muscle mass: +7.5%, p = 0.035; strength: +45%, p = 0.002). BMI and lean body mass increased (p = 0.007). Patients with low BMI showed a better outcome. Intramuscular fat accumulation significantly progressed in spite of ERT (+3.7%, p = 0.001), especially in the poorly responsive posterior thigh muscles. Both clinical assessment and MRI revealed a definite improvement in the anterior thigh muscles. However, progression of intramuscular fat accumulation during ERT, as well as the limited responsiveness of posterior thigh muscles, suggests the necessity for early treatment intervention. The better outcome of patients with low BMI, if confirmed, may indicate that dietary protocols could be adopted as adjuvant measures to ERT in adult GSDII.

Advanced magnetic resonance imaging in benign hereditary chorea: study of two familial cases.

No brain abnormalities are usually detected on conventional magnetic resonance imaging (MRI) in benign hereditary chorea (BHC); there are currently no studies with advanced techniques in literature. We investigated whether conventional and advanced MRI techniques could depict regional brain abnormalities in two familial BHC patients and 24 healthy controls. No brain abnormalities on conventional scans were detectable; also, no significant differences in fractional anisotropy of the basal nuclei were observed. Volumetric analysis showed a decreased volume of the striatum bilaterally compared with controls, whereas spectroscopy demonstrated a significant increased myoinositol/creatine ratio bilaterally, a reduction of choline/creatine ratio bilaterally, and of N-acetyl-aspartate/creatine in the right putamen. With the limits of the small sample size in the patient group, these data show that, despite the absence of macroscopic changes on conventional MRI, volumetric and metabolic abnormalities are present in the basal nuclei of BHC patients.

Electrode displacement after intracerebral hematoma as a complication of a deep brain stimulation procedure.

OBJECTIVES: Deep brain stimulation (DBS) is nowadays considered a safe and effective procedure for various movement disorders in which conservative treatments have failed to show significant therapeutic results. One of the most common complications of definitive electrode positioning is intraparenchymal hemorrhage. MATERIALS AND METHODS: Authors report the case of a 55-year-old female patient treated for Parkinson's disease in which intraparenchymal hemorrhage developed after DBS procedure, leading to significant (about 8 mm at the neuroradiological controls) displacement of an otherwise correctly positioned DBS electrode. RESULTS: After conservative management, the hematoma spontaneously resolved. Late neuroradiological controls documented correct, symmetrically positioned electrodes, comparable to the immediate postoperative controls. CONCLUSIONS: Six months follow-up endpoint results of the DBS treatment were considered satisfying by an independent neurologist, with modest residual neurological deficits, demonstrating that re-positioning of the electrode was unnecessary in this rare complication.

Enzyme replacement therapy in severe adult-onset glycogen storage disease type II.

Glycogen storage disease type II (GSDII) is an autosomal recessive myopathy caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). Enzyme replacement therapy (ERT) with recombinant GAA (rh-GAA) has become available for GSDII, although its effectiveness in adults remains unknown. We present a case of ERT with rhGAA in a 49-year-old male with GSDII in a severe stage of the disease. Quantitative magnetic resonance imaging showed an increase in muscle mass of the inferior limb, especially evident on the quadriceps femoris and the patient's body weight increased up to 30%, although his reported dietary habits were the same as before ERT. Beyond improvement in muscle strength and respiratory function, we observed a dramatic increase in body mass index from 12.7 to 16.6 kg/m(2). This may reflect a change from a catabolic state to a more balanced metabolic state during ERT.