Although migraineurs appear in general to be hypersensitive to external stimuli, they maybe also have increased daytime sleepiness and complain of fatigue. Neurophysiological studies between attacks have shown that for a number of different sensory modalities the migrainous brain is characterised by a lack of habituation of evoked responses. Whether this is due to increased cortical hyperexcitability, possibly due to decreased inhibition, or to an abnormal responsivity of the cortex due a decreased preactivation level remains disputed. Studies using transcranial magnetic stimulation in particular have yielded contradictory results. We will review here the available data on cortical excitability obtained with different methodological approaches in patients over the migraine cycle. We will show that these data congruently indicate that the sensory cortices of migraineurs react excessively to repetitive, but not to single, stimuli and that the controversy above hyper- versus hypo-excitability is merely a semantic misunderstanding. Describing the migrainous brain as 'hyperresponsive' would fit most of the available data. Deciphering the precise cellular and molecular underpinnings of this hyperresponsivity remains a challenge for future research. We propose, as a working hypothesis, that a thalamo-cortical dysrhythmia might be the culprit.

Is The Cerebral Cortex Hyperexcitable or Hyperresponsive in Migraine

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(05)67217-0.pdf

Cluster headache: pathogenesis, diagnosis, and management.

Pupillometry has been one of the most widely used response systems in psychophysiology. Changes in pupil size can reflect diverse cognitive and emotional states, ranging from arousal, interest and effort to social decisions, but they are also widely used in clinical practice to assess patients’ brain functioning. As a result, research involving pupil size measurements has been reported in practically all psychology, psychiatry, and psychophysiological research journals, and now it has found its way into the primatology literature as well as into more practical applications, such as using pupil size as a measure of fatigue or a safety index during driving. The different systems used for recording pupil size are almost as variable as its applications, and all yield, as with many measurement techniques, a substantial amount of noise in addition to the real pupillometry data. Before analyzing pupil size, it is therefore of crucial importance first to detect this noise and deal with it appropriately, even prior to (if need be) resampling and baseline-correcting the data. In this article we first provide a short review of the literature on pupil size measurements, then we highlight the most important sources of noise and show how these can be detected. Finally, we provide step-by-step guidelines that will help those interested in pupil size to preprocess their data correctly. These guidelines are accompanied by an open source MATLAB script (available at https://github.com/ElioS-S/pupil-size). Given that pupil diameter is easily measured by standard eyetracking technologies and can provide fundamental insights into cognitive and emotional processes, it is hoped that this article will further motivate scholars from different disciplines to study pupil size.

/pdf/preprocessing-pupil-size-data-guidelines-and-code-2t6e7h7e1p.pdf

Preprocessing pupil size data: Guidelines and code

A fall in nocturnal plasma melatonin occurs in patients with cluster headache, suggesting that melatonin may play a role in the promotion of attacks. During a cluster period, we administered melatonin to 20 cluster headache patients (2 primary chronic, 18 episodic) in a double-blind placebo-controlled study of oral melatonin 10 mg (n=10) or placebo (n=10) for 14 days taken in a single evening dose. Headache frequency was significantly reduced (ANOVA, p<0.03) and there were strong trends towards reduced analgesic consumption (ANOVA, p<0.06) in the treatment group. Five of the 10 treated patients were responders whose attack frequency declined 3-5 days after treatment, and they experienced no further attacks until melatonin was discontinued. The chronic cluster patients did not respond. No patient in the placebo group responded. There were no side effects in either group. Although the response rate is low, melatonin may be suitable for cluster headache prophylaxis in some patients, particularly those who ca...

Melatonin versus placebo in the prophylaxis of cluster headache : a double-blind pilot study with parallel groups

Cluster headache is a trigeminal autonomic cephalalgia characterised by extremely painful, strictly unilateral, short-lasting headache attacks accompanied by ipsilateral autonomic symptoms or the sense of restlessness and agitation, or both. The severity of the disorder has major effects on the patient's quality of life and, in some cases, might lead to suicidal ideation. Cluster headache is now thought to involve a synchronised abnormal activity in the hypothalamus, the trigeminovascular system, and the autonomic nervous system. The hypothalamus appears to play a fundamental role in the generation of a permissive state that allows the initiation of an episode, whereas the attacks are likely to require the involvement of the peripheral nervous system. Triptans are the most effective drugs to treat an acute cluster headache attack. Monoclonal antibodies against calcitonin gene-related peptide, a crucial neurotransmitter of the trigeminal system, are under investigation for the preventive treatment of cluster headache. These studies will increase our understanding of the disorder and perhaps reveal other therapeutic targets.

Diagnosis, pathophysiology, and management of cluster headache.

Different varieties of pupillary abnormalities have been described in Parkinson's disease but it is not clear if this is due to the disease itself or to the pharmacological treatment. In this study, pupil reactivity to various stimuli (dark/light adaptation, light reflex, near vision reaction and electrical sural stimulation) was investigated in 23de novo parkinsonian patients (not on drugs) to assess pupillary abnormalities and investigate their pathophysiological mechanisms. Parkinsonian patients exhibited larger pupil diameter after light adaptation, as well as a reduced amplitude of contraction and a prolonged contraction time at light reflex. The data obtained confirmed the existence in Parkinson's disease of a pupillary imbalance mainly involving the parasymapathetic system.

Disordered pupil reactivity in Parkinson's disease.

In this study we investigated the variations of pupillary diameter obtained in different experimental conditions (dark/light adaptation, light reflex, sural nerve stimulation) in a group of migraine patients with unilateral location of pain in almost all the attacks and in healthy controls by means of a TV pupillometric device. The data obtained seems to document the existence in migraine of unbalanced vegetative function ascribable either to a strong sympathetic activity or to a parasympathetic deficiency. Moreover, an involvement of central integrative pathways regulating pupil functioning cannot be excluded.

Vegetative imbalance in migraine. A dynamic TV pupillometric evaluation.

Clinical evidences and experimental data on various signs and symptoms of autonomic dysfunction in idiopathic parkinsonism are reported and their characteristics related to the effects of the drugs usually administered for the therapy of the extrapyramidal symptoms. The use of instrumental diagnostic criteria may sometimes help to detect alterations of autonomic functions (micturition disturbances, disorders of pupil reactivity, orthostatic and postprandial hypotension, temperature dysregulation), otherwise not easily identifiable. The existence of a large involvement of autonomic structures both at central and peripheral levels underlines the concept of Parkinson's disease being part of a wide spectrum of degenerative disorders where multiple nervous structures are at risk.

Autonomic disorders in idiopathic parkinsonism.

Iris neuromuscular junction represents a site of reciprocal interactions of sympathetic and parasympathetic innervation and can be considered a useful tool to investigate both systems in physiological and pathological conditions. In this study 35 healthy subjects of different ages were examined by an infrared TV pupillometer to assess darkness and light adaptation, as well as pupillary response to light and to exteroceptive stimulation (RIII reflex). A progressive impairment of pupil adaptability to light stimuli with aging was also observed, while a significant correlation was found between the intensity of electrical stimulation of the sural nerve and the percent increase in pupil diameter. The evaluation of pupil responsiveness is considered for its possible applications in various neurological disorders.

Electronic pupillometry for investigating pupil reactivity to different exteroceptive stimuli: applications and limits.

In this study, a dynamic TV pupillometric system has been used to record the effects of the anticholinergic drug biperidene (Akineton) on pupil responsiveness to various types of stimuli. Plasma levels of the drug were evaluated by means of the radioreceptor binding technique at the same times of pupillometric monitoring. An excellent correlation was found between the effects of biperidene on pupil diameter after light and dark adaptation, light reflex and near vision reaction and the plasma levels of the drug. Radioreceptor binding and dynamic TV pupillometry represent useful tools to evaluate the possible alterations induced by drug therapy on the cholinergic system in man.

Pupillometry and radioreceptor binding. Semeiologic suggestions in the evaluation of the treatment with anticholinergic drugs.

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