Pompe's Disease in Childhood: A Metabolic Myopathy

Background

Myopathy of metabolic origin in childhood occurs due to a variety of conditions. Pompe''s Disease also known as Glycogen storage disease Type II, is a rare storage disorder with clinical presentation akin to spinal muscular atrophy.

Methods

A series of patients with suspected metabolic myopathy were reviewed at a tertiary care service hospital over a period of three years. The diagnosis was confirmed by estimation of acid alpha glucosidase activity.

Result

At our centre, these cases presented with generalized hypotonia, organomegaly (hepatomegaly, cardiomegaly) and congestive cardiac failure. Infantile onset, the most severe form of Pompe''s disease, was the commonest form accounting for 75% of the cases. Four of the babies with infantile onset Pompe''s disease expired, three due to refractory heart failure and one to fulminant respiratory infection before 15 months of age.

Conclusion

Pompe''s Disease is now being increasingly diagnosed, due to definitive enzyme estimation facilities. With the recent availability of enzyme replacement therapy with Myozyme, the prognosis is likely to change for the better.Key Words: Metabolic myopathy, Pompe''s disease, Hypotonia, Cardiomegaly, Hepatomegaly, Acid alpha-glucosidase     

Brain activity is similar during precision and power gripping with light force: an fMRI study

Handgrips can be broadly classified into precision and power grips. To compare central neuronal control of these tasks, functional magnetic resonance imaging was used in 14 healthy right-handed volunteers, who repetitively squeezed non-flexible force transducers with a precision grip and a power grip of the dominant hand. The relative grip force levels and movement rates (0.45 Hertz) of both tasks were comparable. Peak isometric grip forces ranged between 1% and 10% of the maximum voluntary force. Reflecting the additional recruitment of extrinsic hand muscles and the higher absolute force, activation of the contralateral primary sensorimotor cortex (M1/S1) and ipsilateral cerebellum was significantly stronger during power than during precision grip. No brain areas exhibited stronger activity during the precision grip than during the power grip. The left M1/S1 and right cerebellum showed a positive linear relationship with the grip force, while the right angular gyrus and left superior frontal gyrus showed a gradual increase in activity when less force was applied. However, these force-dependent modulations of brain activity were similar for the precision and power grip tasks. No brain region was specifically activated during one task but not during the other. Activity during precision gripping did not exceed the activity associated with power gripping possibly because the precision grip task was not challenging enough to call on dexterous fine motor control.     

The human dorsal premotor cortex facilitates the excitability of ipsilateral primary motor cortex via a short latency cortico-cortical route

In non-human primates, invasive tracing and electrostimulation studies have identified strong ipsilateral cortico-cortical connections between dorsal premotor- (PMd) and the primary motor cortex (M1(HAND) ). Here, we applied dual-site transcranial magnetic stimulation (dsTMS) to left PMd and M1(HAND) through specifically designed minicoils to selectively probe ipsilateral PMd-to-M1(HAND) connectivity in humans. A suprathreshold test stimulus (TS) was applied to M1(HAND) producing a motor evoked potential (MEP) of about 0.5 mV in the relaxed right first dorsal interosseus muscle (FDI). A subthreshold conditioning stimulus (CS) was given to PMd 2.0-5.2 ms after the TS at intensities of 50-, 70-, or 90% of TS. The CS to PMd facilitated the MEP evoked by TS over M1(HAND) at interstimulus intervals (ISI) of 2.4 or 2.8 ms. There was a second facilitatory peak at ISI of 4.4 ms. PMd-to-M1(HAND) facilitation did not change as a function of CS intensity. Even at higher intensities, the CS alone failed to elicit a MEP or a cortical silent period in the pre-activated FDI, excluding a direct spread of excitation from PMd to M1(HAND). No MEP facilitation was present while CS was applied rostrally over lateral prefrontal cortex. Together our results indicate that our dsTMS paradigm probes a short-latency facilitatory PMd-to-M1(HAND) pathway. The temporal pattern of MEP facilitation suggests a PMd-to-M1(HAND) route that targets intracortical M1(HAND) circuits involved in the generation of indirect corticospinal volleys. This paradigm opens up new possibilities to study context-dependent intrahemispheric PMd-to-M1(HAND) interactions in the intact human brain.     

White matter microstructural changes of thalamocortical networks in photosensitivity and idiopathic generalized epilepsy

Purpose: Photosensitivity or photoparoxysmal response (PPR) is an electroencephalography trait that is highly associated with idiopathic generalized epilepsies (IGEs) and characterized by changes in cortical excitability in response to photic stimulation. Studying functional and structural changes of PPR might provide important insights into the pathogenesis of IGE. Recent studies revealed a functional network consisting of occipital, parietal, and precentral areas that might be implicated in PPR. Herein, we investigate the microstructural changes associated with PPR. Methods: Twelve healthy subjects with PPR, nine patients with IGE and PPR (IGE‐PPR group), and 18 healthy controls were studied with diffusion magnetic resonance imaging. Tract‐based spatial statistics were used to test for regional differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, and radial diffusivity between groups. Key Findings: Subjects with PPR exhibited higher FA in the right precentral juxtacortical white matter and higher MD in lateral occipital areas relative to controls. Patients with IGE‐patients showed additional increases in regional FA in the thalamus and juxtacortical precentral and parietal areas. Both subjects with PPR and patients with IGE‐PPR presented axial and radial diffusivity changes in the occipital regions. Significance: Our results show that PPR is associated with subcortical microstructural changes in precentral, parietal, and occipital regions. The coexistence of PPR and IGE is associated with white matter abnormalities in the thalamus and precuneus. PPR and epilepsy share similar functional and structural networks in widespread cortical and subcortical areas.     

Aging is associated with contrasting changes in local and distant cortical connectivity in the human motor system

Pathophysiological changes in neurological and neuropsychiatric diseases are increasingly described in terms of abnormal network connectivity. However, the anatomical integrity and efficacy of connections among multiple brain regions change with aging, even in healthy adults. We combined low-frequency transcranial magnetic stimulation and positron emission tomography to study the age-related changes in regional activation and effective connectivity, associated with voluntary action by healthy adults between 22 and 68 years old. Contrasting effects of aging on the motor network were seen using analyses of regional activation, effective connectivity mediating task-related neuronal activation and effective connectivity in response to transcranial magnetic stimulation. Low-frequency rTMS reduced cerebral blood flow during both movement and resting conditions, at the site of stimulation and neighboring frontal cortex. Aging was associated with increased movement-related activation in premotor cortex, bilaterally. Increasing age also increased the susceptibility of the cortex to the inhibitory effects of rTMS, at the site of stimulation and its contralateral homologue. Moreover, older subjects showed enhanced local effective connectivity, centered on the left premotor cortex, but reduced effective connectivity between distant motor-related cortical areas. We discuss these results in relation to the HAROLD model of aging and propose that there are differential effects of aging on local and distributed neuronal subpopulations in the motor network. This differential effect of aging has important implications for the study of neurodegenerative and cerebrovascular diseases that primarily affect older people, as well as our understanding of the normal aging process.