JAMA Neurology: Neurology Topic Collection

Clinical and Biochemical Differences in Patients Having Parkinson Disease With vs Without GBA Mutations Patients Having PD With vs Without GBA Mutations

Chahine LM, Qiang J, Ashbridge E, et al. — Mon, 13 May 2013 00:00:00 GMT

Importance

Biochemical abnormalities present in GBA (mut/wt) carriers may offer new pathogenetic insights to and potential therapeutic targets in Parkinson disease (PD).

Objective

To determine whether patients having PD with vs without GBA mutations differ in clinical phenotype or plasma protein expression.

Design and Setting

Case-control study of patients having PD with vs without GBA mutations. Clinical characteristics were compared between groups, and biochemical profiling of 40 plasma proteins was performed to identify proteins that differed in expression between groups.

Participants

The discovery cohort included 20 patients having PD with GBA mutations. Clinical characteristics of GBA -associated PD cases were compared with those of 242 patients having PD in whom GBA mutations were excluded by full gene sequencing.

Main Outcome Measures

Biochemical profiling was available for all 20 GBA -associated PD cases, as well as a subset (87 of 242) of the GBA -negative PD cases. The replication cohort included 19 patients having PD with GBA mutations and 41 patients having PD without GBA mutations.

Results

Compared with patients having PD without GBA mutations, patients having PD with GBA mutations were younger at disease onset (P = .04) and were more likely to demonstrate cognitive dysfunction (P = .001). In a multiple regression model that included age, sex, and assay batch as covariates, GBA mutation status was significantly associated with plasma levels of interleukin 8 (P = .001), monocyte chemotactic protein 1 (P = .008), and macrophage inflammatory protein 1α (P = .005). The association between interleukin 8 and GBA mutation status was replicated (P = .03) in a separate cohort of patients having PD with vs without GBA mutations.

Conclusions and Relevance

Patients having PD with GBA mutations have earlier age at disease onset and are more likely to demonstrate cognitive dysfunction. Monocyte-associated inflammatory mediators may be elevated in patients having PD with GBA mutations.

Autoantibodies in Sporadic Creutzfeldt-Jakob Disease Autoantibodies/Sporadic Creutzfeldt-Jakob Disease

Angus-Leppan H, Rudge P, Mead S, et al. — Mon, 13 May 2013 00:00:00 GMT

Importance

The diagnosis of autoimmune and neurodegenerative conditions can be unclear. Treatments such as removing the associated tumor, if present, and immunosuppression can halt or often reverse the progression of autoimmune conditions, but there is no curative treatment for neurodegenerative conditions. The presence of autoantibodies can sometimes be misleading. This report illustrates potential difficulties in differentiating autoimmune encephalopathies from sporadic Creutzfeldt-Jakob disease.

Observations

In a clinical follow-up of an older man with rapidly evolving encephalopathy at a neuroscience center, unsuccessful treatment with immunosuppression based on the incorrect presumptive diagnosis of Morvan syndrome was followed by the correct histological diagnosis of sporadic Creutzfeldt-Jakob disease.

Conclusions and Relevance

Autoimmune encephalopathies raise important treatment options and potential for recovery. However, since neuronal antibodies may be positive in prion disease, interpretation can be complex and must be rooted in the clinical picture.

Emergency Management of Acute Ischemic Stroke The Evolving Roles of Intravenous and Endovascular Therapies Emergency Management of Acute Ischemic Stroke

Adams HP, Froehler MT. — Mon, 13 May 2013 00:00:00 GMT

In 1996, the US Food and Drug Administration approved the use of intravenous recombinant tissue plasminogen activator (rtPA) for the treatment of carefully selected patients with acute ischemic stroke who could receive the medication within 3 hours of onset of symptoms. Since that time, the maximum time window for treatment has been expanded to 4.5 hours. Guidelines are available to provide recommendations and advice for the use of intravenous rtPA. As a result, rtPA has revolutionized the care of patients with ischemic stroke; now, patients with stroke may be successfully treated, and outcomes may be improved. Intravenous thrombolysis is now the engine that is driving emergency stroke care.

TRIM Proteins in Therapeutic Membrane Repair of Muscular Dystrophy TRIM Proteins in Muscular Dystrophy

Alloush J, Weisleder N. — Mon, 13 May 2013 00:00:00 GMT

Muscular dystrophy represents a major unmet medical need; only palliative treatments exist for this group of debilitating diseases. Because multiple forms of muscular dystrophy arise from compromised sarcolemmal membrane integrity, a therapeutic approach that can target this loss of membrane function could be applicable to a number of these distinct diseases. One promising therapeutic approach involves the process the cell uses to repair injuries to the plasma membrane. Recent discoveries of genes associated with the membrane repair process provide an opportunity to promote this process as a way to treat muscular dystrophy. One such gene is mitsugumin 53 (MG53), a member of the tripartite motif (TRIM) family of proteins (TRIM72), which is an essential component of the membrane repair pathway in muscle. Recent results indicate that MG53/TRIM72 protein can be directly applied as a therapeutic agent to increase membrane repair capacity of many cell types and treat some aspects of the disease in mouse models of muscular dystrophy. There is great potential for the use of recombinant human MG53 in treating muscular dystrophy and other diseases in which compromised membrane integrity contributes to the disease. Other TRIM family proteins may provide additional targets for therapeutic intervention in similar disease states.