It's the holidays, traditionally a time to focus on the things that make us happy. Raindrops on roses and whiskers on kittens, that sort of thing. Maybe it's Grinch-like of me, but on this holiday weekend I'm writing about what I think is actually my least favorite thing... brain cancer. How like cancer to come when least welcome.
I've seen a lot of bad diseases in neurology, and I can't even definitively say that brain tumors are the worst of them, but for some reason there's something about cancer that particularly frustrates and angers me. Maybe it's a sense of betrayal by one's own body. Maybe it's that so many cancers have resisted our best efforts to treat them. Maybe it's that brain cancer seems so indiscriminate in its victims.
The real problem begins in gliomas, when the glial cells meant to support neurons go bad. Even here, some gliomas are better than others. Oligodendrogliomas are often more treatment responsive than many astrocytomas, for example. The worst of the primary brain tumors is grade IV astrocytoma, also known as glioblastoma multiforme, or GBM.
There is some glimmer of hope, though. Genetic markers can label which malignant gliomas respond better to particular treatments, hopefully heralding a time of more targeted therapies with fewer toxic side effects. For those with these aggressive tumors, such personalized medicine cannot come quickly enough.
Facial Onset Sensory and Motor Neuronopathy (FOSMN) is a very rare disorder. In fact, fewer than 20 cases have been reported in the scientific literature so far, including the cases described in 2006, when the syndrome was first described. Briefly, patients first developed paresthesia and numbness in the face, which then spread to the scalp, neck, arms and upper trunk. Later, cramps, fasciculations, and slurred speech developed. Autopsy was done on one patient in 2006, which showed loss of neurons in the brainstem and spinal cord in a fashion similar to amyotrophic lateral sclerosis, though also impacting sensory nerves. The disease seems quite serious, as patients lose their ability to speak or swallow safely. The cause is unknown, though some have suggested a possible autoimmune component, as one case has responded to immunotherapy.
Hokonohara T, Shigeto H, Kawano Y et al. Facial onset sensory and motor neuronopathy (FOSMN) syndrome responding to immunotherapies. Journal of the Neurological Sciences. (Vol. 275, Issue 1, Pages 157-158
Vucic S, Tian D, Siao Tick Chong P, et al. Facial onset sensory and motor neuronopathy (FOSMN syndrome) a novel syndrome in neurology. Brain (Vol. 129, Issue 12, Pages 3384-3390)
Neurologists like to figure out where things come from. Specifically, if there is a symptom, we like to find a place in the nervous system that is necessary for that symptom to occur.
Sometimes this leads to thinking that is oversimplified. The brain is complicated, and so are our thoughts and feelings. To say that there is one spot in the brain for such a thing as gratitude, for example, would be misleading.
That said, there are regions of the brain that are needed for something like gratitude to occur, and researchers recently described one such area.
The researchers investigated over 60 healthy people by giving them a task in which they were to describe their response to interacting with a friend in different scenarios This allowed the researchers to assign a scale as to how likely the participant was to describe the scenario in a prideful, grateful, guilty or angry fashion. MRI scans of all the participants were then compared.
People who were more likely to respond in a grateful fashion had increased volume in the right temporal lobe. This area has been found to be diminished in a subtype of frontotemporal dementia, a disease that slowly robs people of their normal personality. The right temporal type of frontotemporal dementia frequently leads to colder and less empathetic personality changes.
The authors also found that the posterior cortex, normally associated with visualization, also seemed to be important in moral sentiment such as gratitude. This may be due to a need to imagine a scenario clearly in order to generate empathy, for example.
The overlap between regions of the brain normally associated with empathy and areas associated with gratitude is interesting to me. Perhaps this region actually just stores information regarding social rules in general? Or maybe a degree of empathy is necessary in order to feel grateful-- for example, in order to recognize what giving you something has cost someone else.
Roland Zahn,Griselda Garrido, Jorge Moll, and Jordan Grafman. Individual differences in posterior cortical volume correlate with proneness to pride and gratitude.Social Cognitive and Affective Neuroscience Advance Access, epub October 28, 2013
Tardive syndromes (TDS) consist of abnormal involuntary abnormal movements, usually associated with at least 3 months total cumulative exposure to neuroleptic medication. The syndromes are especially common in schizophrenia, as the drugs that treat schizophrenia often have this side effect. Up to 30% of people with schizophrenia have these abnormal movements.
The disorder can be very difficult to treat. Even withdrawing the neuroleptic medication has unclear benefits, as schizophrenic symptoms may worsen and the abnormal movements may not improve. Switching to another class of medication such as atypical antipsychotics is often done, as these have less chance of causing TDS, but there's not enough evidence to say for sure. Several different medications are used to try to control these symptoms. In short, clonazepam and ginkgo biloba probably improve TDS. Risperidone may improve TDS, but should not be considered as treatment because even while it improves symptoms, i tmay make the underlying problem worse. Amantadine and tetrabenazine can also be considered. A number of different things have been tried but are considered to have insufficient evidence, including acetazolamide, bromocritpine, thiamine, baclofen, vitamin E, vitamin B6, selegilene, clozapine, olanzapine, melatonin, thiopropazate, haldoperidol, leviteracetam, quetiapine, ziprazidone, aripiprazole, buspirone, yi-gan san, botulinum toxin a, electroconvulsive therapy, alpha-methyldopa, reserprine, and pallidal deep brain stimulation.
Ghidayasiri, R Fahn S, Weiner, W et al. Evidence based guideline: Treatment of tardive syndromes report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology (2013) 81:5, 463-469.
Surgical treatments have long been recognized for treating movement disorders such as essential tremor, but are not widely used due to the inherent risks of neurosurgery. A recent paper describes a noninvasive technique that uses ultrasound to ablate the ventralis intermedius nucleus of the thalamus without the need of cutting through the skull. Of the 15 patients who underwent the small pilot study, all described a benefit. These results are not conclusive, and a larger placebo control needs to take place to confirm findings. If true, however, this would present an exciting option for those whose essential tremor is not fully controlled with medication.
Elias WJ, Huss D, Wintermark M et al. A pilot study of focused ultrasoundthalamotomy for essential tremor. N Engl J Med 2013;369:640-8
Lipsman N, Schwartz ML, Lozano AM. MR-guided focused ultrasound thalamotomy for essential tremor: a proof-of-concept study. Lancet Neurol 2013;12(5): 462-468
Torres DM, Galetta KM, Phillips HW et al. Sports-related concussion: anonymous survey of a collegiate cohort. Neurology: Clinical Practice, August 2013, pg 279-286
Scientists have thought for a long time that disorders like Parkinson's may, in fact, be more than one disease. Researchers recently found more evidence to support this.
Parkinson's disease results from a misfolded protein called alpha-synuclein. Two different types of alpha-synuclein were demonstrated, and they demonstrated that one form was more highly toxic than the other.
These results may suggest why some forms of Parkinson's are more aggressive than others, why symptoms vary between different people, or why medication has varying effects.
Bousset L, Pieri L, Ruiz-Arlandis L, Structural and functional characterization of two alpha-synuclein strains. Nature Communications, epub October 10, 2013
Perhaps the worst thing about much of neurology is the not knowing. Is a headache just tension or is it something serious like a blood clotor tumor? pain. Is your difficulty remembering things normal aging, something reversible like Hashimoto's encephalopathy, or a dementia like Alzheimer's disease?
As a doctor, I want to offer patients hope while also remaining realistic. I want to reassure, even in the face of terrifying disease, while staying honest. What's the best way for a doctor to ease the fears of a patient and their family?
Can the dead really walk among us? Not only do some people claim this to be true--they claim to be dead themselves.
The Cotard delusion is a rare disorder in which someone believes themselves to be dead or otherwise nonexistent. Such people usually become withdrawn from friends and family members, and may neglect caring for themselves. This disorder is named after a French neurologist who described the delusion in 1880.
Cotard described a patient who denied that several parts of her body existed. She also stated that she was damned for eternity, and couldn't die a natural death. She ultimately died of starvation.
The Cotard delusion may be part of a psychotic disorder such as schizophrenia, and has also been described after brain injury. The exactly location of the brain injury may vary. Some relate the delusion to the parietal lobes, and others to the median frontal lobe.
The delusion has been shown to often respond to pharmacological treatment with psychiatric medications. Electroconvulsive therapy may also be effective.
Berrios G.E. and Luque R. (1995) Cotard Syndrome: clinical analysis of 100 cases. Acta Psychiatrica Scandinavica 91: 185-188
Berrios G.E. & Luque R. (1999) Cotard's 'On hypochondriacal delusions in a severe form of anxious melancholia'. History of Psychiatry 10: 269-278.