4 Exciting Neurology Papers from 2014

In November, Beutler et al, showed that among a cohort of patients examined for neuropathy in response to chemotherapy agents, specifically paclitaxel, those with severe peripheral neuropathy had an increased representation of mutant alleles in known Charcot-Marie-Tooth genes. This suggests that these types of mutations may predispose patients to develop neuropathy in response to chemotherapy. There are some significant implications from this work: (A) Should patients be screened for such mutations before exposure to chemotherapy? (B) Are similar risk factors related to other symmetric polyneuropathy causes, such as diabetes?Details here.

An association between smoking and PD has long been speculated because smokers are underrepresented among PD patients. This led many to suspect that nicotine might be protective. A recent study by Ritz et al provided an interesting new idea about this. The authors examined a cohort of patients who quit smoking and determined whether they were more or less likely to develop PD. It turns out that patients who went on to develop PD had an easier time quitting smoking, and thus smokers are less represented among PD patients. This suggests that perhaps instead of smoking being protective, it may be that PD patients have presymptomatic alterations in their reward circuitry that makes smoking less addictive. This will be interesting to follow in future studies.
• Ritz B, Lee PC, Lassen CF, Arah OA. Parkinson disease and smoking revisited: ease of quitting is an early sign of the disease. Neurology. 2014;83:1396-1402Details here.

In recent years, the existence of fairly common neuropsychiatric syndromes associated with NMDA receptor associated antibodies has become clear. Many such patients are now recognized and successfully treated with immunosuppressive therapies. Why is this syndrome reversible and why do patients get better? A recent paper by Moscato et al showed that these antibodies lead to endocytic removal of the receptors from the cell surface. This leads to downregulation of NMDA receptors on the cell surface and impaired neurotransmission. When these receptors are lost on interneurons, this may well be the cause of seizures. This suggests that the syndrome may be fairly rapidly reversible because removal of the antibodies should lead to return of newly expressed receptors to the cell surface.
• Moscato EH, Peng X, Jain A, et al. Acute mechanisms underlying antibody effects in anti-N-methyl-D-aspartate receptor encephalitis. Ann Neurol. 2014;76:108-119.Details here.

In multiple sclerosis, the focus is on the appearance of new lesions with associated new hard neurologic findings. The inciting event for a new attack is still far from clear because it is quite difficult to study what is happening before an attack in a given patient. A recent paper by Maggi et al sheds light on this. The authors studied an animal model of MS that is quite faithful to the disease-chronic relapsing experimental allergic encephalomyelitis in primates-and performed serial 7 Tesla MRI imaging. They found that before a new lesion appears there is already some breakdown of the blood brain barrier with increased vascular permeability in the region where the lesion will appear for up to 4 weeks prior to a new lesion being visible. They correlated this with pathology and found perivascular inflammation and microglial activation before the recruitment of blood-borne immune cells. This is further suggestion that immune responses active inside the CNS are responsible for the appearance of lesions and that what is usually seen in MRIs of patients is the result of a cascade that starts well before the lesion appears clinically and radiologically using routine imaging.
• Maggi P, Macri SM, Gaitán MI, et al. The formation of inflammatory demyelinated lesions in cerebral white matter. Ann Neurol. 2014;76:594-608Details here.