New diagnostic tools, new therapies, new preventive approaches for neurodegenerative diseases… There were many interesting uplifting findings in April. But as always, there were also not so good news. Here are the best and worst with which I came across in April. Comments are welcome!

THE BEST

BEST: A new diagnostic tool for Lewy body disorders

Lewy body disorders are highly misdiagnosed, particularly at early disease stages, mostly because of their symptoms’ close resemblance with Alzheimer’s disease. This has been a huge obstacle to the development of effective therapies. With the goal of improving the diagnostic accuracy of Parkinson’s disease and other Lewy body dementias, a new study published in the Journal of Parkinson’s Disease investigated the viability of assessing the accumulation of synuclein in the submandibular glands of subjects with Lewy Body disorders as a diagnostic tool.

It was shown that Lewy-type synucleinopathy was found in the submandibular gland of 89% of Parkinson’s disease subjects, and in 71% of subjects with Dementia with Lewy Bodies, whereas other types of dementia showed very low levels of synuclein accumulation in the submandibular gland.  These results therefore present submandibular gland biopsy as a potential new tool for the accurate diagnostic of Parkinson’s disease and Dementia with Lewy Bodies.

BEST: Botulinum toxin A for the treatment of neuropathic pain

New applications for botulinum toxin A keep being reported. There have been indications of a potential analgesic effect of botulinum toxin A in peripheral neuropathic pain, but the available data was still largely inconsistent. In a new study published in The Lancet Neurology, the safety and efficacy of repeated administrations of botulinum toxin A in patients with neuropathic pain was assessed.

It was found that the administrations of botulinum toxin can have a sustained analgesic effect against peripheral neuropathic pain, being able to reduce pain intensity over 24 weeks.

BEST: Molecular therapy for spinal cord injury

Functional recovery after spinal cord injury is hard and limited. But a new study published in Nature Neuroscience brings new hope to spinal cord injury treatment.

By interfering with the expression of a molecule that controls the growth of axons, the researchers were able to recover motor functions in mice with a partial cervical dorsal column lesion. The recovery was not only more effective, but also faster. However, in the absence of regular training, functional recovery was compromised. These results show that molecular manipulation in association with targeted physical rehabilitation may hold promise as a therapy for spinal cord injury.

BEST: Using antibodies to prevent Alzheimer’s disease

Immunization against misfolded toxic proteins is a promising approach to treat neurodegenerative disorders. In the case of Alzheimer’s disease, clinical data indicates that antibodies directed against the amyloid-beta peptide should be administered before the onset of symptoms associated with irreversible brain damage. A study published in Brain tested the efficacy of a bioactive implant consisting of encapsulated cells genetically engineered to secrete high levels of anti-amyloid-beta antibodies.

It was shown that these antibodies were able to penetrate the brain and bind amyloid plaques in mice with Alzheimer’s. When these antibody-producing encapsulated cells were implanted before the onset of amyloid plaque deposition, there was a marked reduction in amyloid-beta levels and amyloid plaque formation in the brain. Furthermore, phospho-tau pathology in the hippocampus was also prevented. This therapeutic approach may potentially aid in hampering the development of Alzheimer’s disease, if applicable to humans.

BEST: Neurologic music therapy for Parkinson’s disease

Gait disturbance and balance disorders are common symptoms of Parkinson’s disease. In a pilot study published in Frontiers in Human Neuroscience, the effect of the combination of all three Neurologic Music Therapy sensorimotor techniques – Therapeutic Instrumental Music Performance, Pattern Sensory Enhancement and Rhythmic Auditory Stimulation – on gait and posture in the course of Parkinson’s disease were assessed.

Data showed that the combination of the three techniques was able to significantly improve gait and the sense of body position and movement, as well as other rhythmical activities in Parkinson’s disease rehabilitation.

THE WORST

WORST: Beware of sleep disturbances after traumatic brain injury

Traumatic brain injury is often associated with sleeping problems. And these problems may still be present a long time after the occurrence of the injury, according to a study published in Neurology.

These post-traumatic sleep–wake disturbances are commonly disregarded by patients, but they may actually exacerbate other outcomes of traumatic brain injury, and affect the patients’ quality of life. Eighteen months after the injury, an excessive daytime sleepiness was determined in 67% of patients with brain trauma.

WORST: A causal link between Zika virus and microcephaly

Scientists from the Centers for Disease Control and Prevention (CDC) have reached the conclusion that the Zika virus is indeed a cause of microcephaly and other developmental brain defects. In a special report published in The New England Journal of Medicine, the existing evidence establishing a link between the Zika virus and neurodevelopmental disorders was reviewed, leading to the aforementioned conclusion.

The reviewed evidence showed that the timings of Zika virus infection were consistent with the type of developmental defects observed. Furthermore, Zika virus was identified in the brain tissue of affected fetuses and infants.

WORST: Zika virus can also trigger Guillain–Barré syndrome

A report published in The Lancet adds to the list of neurological disorders induced by the Zika virus. According to observations from French Polynesia during a Zika outbreak in 2013-2014, the virus can also trigger Guillain–Barré syndrome, a serious neurological disorder that causes progressive muscle weakness and, ultimately, respiratory failure. At the time of the Zika virus outbreak, a remarkable increase in Guillain–Barré syndrome was observed in the area. Among the patients diagnosed with GBS, 88% reported having been ill about 1 week before the onset of neurological symptoms and 98% of them had antibodies against the Zika virus.

Given the fast spreading of the Zika virus in South America, this study serves as an alert to the possibility of a similar increase in Guillain-Barré syndrome associated with the Zika virus.

WORST: The long-term effects of an early intervention for PTSD

Early treatment for post-traumatic stress disorder (PTSD) helps most people with this condition achieve a faster recovery. However, the long-term effects of this early intervention remained to be determined. Therefore, the 3-year outcome of early interventions to individuals with acute PTSD were evaluated.

The results were published in The Journal of Clinical Psychiatry and confirmed that an early intervention with prolonged exposure and cognitive therapy significantly reduced PTSD symptoms between 1 and 5 months. However, after 3 years, patients had similar levels of PTSD symptoms, similar prevalence of PTSD, and similar secondary outcomes. This work demonstrates that although early intervention is helpful for PTSD patients, it does not reduce the 3-year prevalence of the disorder. This highlights the need for more effective long-term interventions for PTSD.

WORST: The link between dementia and diabetes

There is an increased awareness of an association between diabetes and dementia. Given that insulin signaling in the brain can regulate carbohydrate, lipid, and branched chain amino acid metabolism in the liver and adipose tissue, for example, it was hypothesized that neurodegeneration could impair the brain’s metabolic control through disruption of insulin signaling, leading to an increased susceptibility to diabetes. To test this hypothesis, the authors of the work published in Alzheimer’s & Dementia used mice with Alzheimer’s disease which were fed a high-fat diet or were subjected to aging-induced metabolic dysregulation.

The results indicated that Alzheimer’s disease does indeed increase susceptibility to diabetes due to impaired insulin signaling in the hypothalamus.

References

Attal, N., de Andrade, D., Adam, F., Ranoux, D., Teixeira, M., Galhardoni, R., Raicher, I., Üçeyler, N., Sommer, C., & Bouhassira, D. (2016). Safety and efficacy of repeated injections of botulinum toxin A in peripheral neuropathic pain (BOTNEP): a randomised, double-blind, placebo-controlled trial The Lancet Neurology, 15 (6), 555-565 DOI: 10.1016/S1474-4422(16)00017-X

., Beach, T., Adler, C., Serrano, G., Sue, L., Walker, D., Dugger, B., Shill, H., Driver-Dunckley, E., Caviness, J., Intorcia, A., Filon, J., Scott, S., Garcia, A., Hoffman, B., Belden, C., Davis, K., & Sabbagh, M. (2016). Prevalence of Submandibular Gland Synucleinopathy in Parkinson’s Disease, Dementia with Lewy Bodies and other Lewy Body Disorders Journal of Parkinson’s Disease, 6 (1), 153-163 DOI: 10.3233/JPD-150680

Bukowska, A., Kr??a?ek, P., Mirek, E., Bujas, P., & Marchewka, A. (2016). Neurologic Music Therapy Training for Mobility and Stability Rehabilitation with Parkinson’s Disease – A Pilot Study Frontiers in Human Neuroscience, 9 DOI: 10.3389/fnhum.2015.00710

Cao-Lormeau, V., Blake, A., Mons, S., Lastère, S., Roche, C., Vanhomwegen, J., Dub, T., Baudouin, L., Teissier, A., Larre, P., Vial, A., Decam, C., Choumet, V., Halstead, S., Willison, H., Musset, L., Manuguerra, J., Despres, P., Fournier, E., Mallet, H., Musso, D., Fontanet, A., Neil, J., & Ghawché, F. (2016). Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study The Lancet, 387 (10027), 1531-1539 DOI: 10.1016/S0140-6736(16)00562-6

Hollis, E., Ishiko, N., Yu, T., Lu, C., Haimovich, A., Tolentino, K., Richman, A., Tury, A., Wang, S., Pessian, M., Jo, E., Kolodkin, A., & Zou, Y. (2016). Ryk controls remapping of motor cortex during functional recovery after spinal cord injury Nature Neuroscience, 19 (5), 697-705 DOI: 10.1038/nn.4282

Imbach, L., Buchele, F., Valko, P., Li, T., Maric, A., Stover, J., Bassetti, C., Mica, L., Werth, E., & Baumann, C. (2016). Sleep-wake disorders persist 18 months after traumatic brain injury but remain underrecognized Neurology DOI: 10.1212/WNL.0000000000002697

Lathuilière, A., Laversenne, V., Astolfo, A., Kopetzki, E., Jacobsen, H., Stampanoni, M., Bohrmann, B., Schneider, B., & Aebischer, P. (2016). A subcutaneous cellular implant for passive immunization against amyloid-? reduces brain amyloid and tau pathologies Brain, 139 (5), 1587-1604 DOI: 10.1093/brain/aww036

Rasmussen, S., Jamieson, D., Honein, M., & Petersen, L. (2016). Zika Virus and Birth Defects — Reviewing the Evidence for Causality New England Journal of Medicine DOI: 10.1056/NEJMsr1604338

Ruiz, H., Chi, T., Shin, A., Lindtner, C., Hsieh, W., Ehrlich, M., Gandy, S., & Buettner, C. (2016). Increased susceptibility to metabolic dysregulation in a mouse model of Alzheimer’s disease is associated with impaired hypothalamic insulin signaling and elevated BCAA levels Alzheimer’s & Dementia DOI: 10.1016/j.jalz.2016.01.008

Shalev, A., Ankri, Y., Gilad, M., Israeli-Shalev, Y., Adessky, R., Qian, M., & Freedman, S. (2016). Long-Term Outcome of Early Interventions to Prevent Posttraumatic Stress Disorder The Journal of Clinical Psychiatry DOI: 10.4088/JCP.15m09932

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