Outcome measures and treatment effectiveness in late onset myasthenia gravis.

BACKGROUND: Recently different subtypes of myasthenia gravis (MG) have been described. They differ for clinical features and pathogenesis but the prognosis and response to treatment is less clear. The aim of the study was to evaluate outcome and treatment effectiveness including side effects in late onset MG (LOMG) compared with early onset MG (EOMG). METHODS: We analysed retrospectively 208 MG patients. Clinical features were recorded as well as treatment and side effects. Outcome at the last follow-up was evaluated with MGSTI and MGPIS scales. RESULTS: The 208 patients included were classified as follow: 36 ocular MG, 40 EOMG, 72 LOMG, 25 thymoma-associated, 14 anti-MuSK and 21 double seronegative. Similar positive outcome was achieved in either early and late onset subgroup. We found pharmacological remission and minimal manifestations at the MGFA-PIS in the 95% and 94,4% of EOMG and LOMG respectively but in LOMG a lower dose of immunosuppressors (MGSTI< 2) was required compared to EOMG (p = 0,048). Severe side effects were present in a small percentage of patients in both group but diabetes was more frequent in LOMG vs EOMG (2,2% vs 5%, p = 0.017). CONCLUSIONS: Despite LOMG has more comorbidities that might interfere with treatment and outcome, therapeutic management does not seem to differ between EOMG and LOMG. A similar positive outcome was seen in both subgroups but LOMG group seems to require lower doses of medication to control symptoms.

Ataxia in posterior circulation stroke: clinical-MRI correlations.

OBJECTIVE: Ataxia is characterized clinically by four signs (gait and limb ataxia, dysarthria and nystagmus). Although ataxia has been described in posterior circulation (PC) stroke series, there are no prospective studies that have investigated a possible differential role of the cerebellum or its input/outputs in causing ataxia. METHODS: Ataxia was semi-quantified according to the International Cooperative Ataxia Rating Scale (ICARS) in 92 consecutive patients with acute PC stroke. Four topographical patterns based on magnetic resonance imaging (MRI) findings were identified: picaCH pattern (posterior inferior cerebellar artery infarct); scaCH pattern (superior cerebellar artery infarct); CH/CP pattern (infarct involving both the cerebellum and the brainstem cerebellar pathways); and CP pattern (infarct involving the brainstem cerebellar pathways). RESULTS: Gait ataxia was present in 95.7%, limb ataxia in 76.1%, dysarthria in 56.5% and nystagmus in 65.2% of patients. Gait ataxia frequency did not differ between the patterns, but was significantly more severe in the CH/CP pattern than in either picaCH (P=0.0059) or CP (P=0.0065) pattern. Limb ataxia was significantly less frequent (P<0.001) and less severe (P<0.001) in picaCH pattern than other patterns. Dysarthria was less frequent in picaCH pattern than in other patterns (P=0.018) and less severe than in scaCH (P=0.0043) or CP (P=0.0047) pattern. No differences in nystagmus frequency or severity were observed across all four patterns. CONCLUSION: In PC stroke gait ataxia was almost always present, regardless of the lesion site. Limb ataxia and dysarthria were less frequent in the picaCH pattern, whereas nystagmus, when present, did not differ among the topographical patterns.

Structural and functional anatomy of the globular domain of complement protein C1q.

C1q is the first subcomponent of the classical pathway of the complement system and a major connecting link between innate and acquired immunity. As a versatile charge pattern recognition molecule, C1q is capable of engaging a broad range of ligands via its heterotrimeric globular domain (gC1q) which is composed of the C-terminal regions of its A (ghA), B (ghB) and C (ghC) chains. Recent studies using recombinant forms of ghA, ghB and ghC have suggested that the gC1q domain has a modular organization and each chain can have differential ligand specificity. The crystal structure of the gC1q, molecular modeling and protein engineering studies have combined to illustrate how modular organization, charge distribution and the spatial orientation of the heterotrimeric assembly offer versatility of ligand recognition to C1q. Although the biochemical and structural studies have provided novel insights into the structure-function relationships within the gC1q domain, they have also raised many unexpected issues for debate.