Chronic migraine is a neurological disorder characterized by 15 or more headache days per month of which at least 8 days show typical migraine features. The process that describes the development from episodic migraine into chronic migraine is commonly referred to as migraine transformation or chronification. Ample studies have attempted to identify factors associated with migraine transformation from different perspectives. Understanding CM as a pathological brain state with trigeminovascular participation where biological changes occur, we have completed a comprehensive review on the clinical, epidemiological, genetic, molecular, structural, functional, physiological and preclinical evidence available.
Reviewer 1: Did the patient improve at all after radiation? Practicing clinicians may want to know. Desmoplastic cancers of all types, including mesothelioma, are not as responsive to this modality. Were steroids administered and did they help as well?We agree that desmoplastic mesothelioma cells are only modestly radiosensitive. Our patient was treated with radiation therapy (25Gy on the primary MM tumor and 20Gy on the spinal metastasis) instead of second-line systemic therapy because of the rather localized aspect of malignant disease and to achieve additional pain control in his right shoulder/neck. Steroids (methylprednisolone 16mg/day for 1 week and methylprednisolone 8mg/day for 1 week) were added during the radiation therapy as an adjunctive anti-inflammatory treatment. There was no significant clinical improvement after this therapy and repeat CT one month later showed stable disease. In the months thereafter, his neurological status deteriorated and he received best supportive care.Reviewer 2: Dr. Ralki and colleagues present an interesting case of desmoplastic mesothelioma with spine metastases causing neurologic symptoms. While the ability of mesothelioma to metastasize distantly is well recognized, it is not reflected well in the literature and this case report thoughtfully adds to that literature. My only comment would be to more specifically discuss what has been reported about this for mesothelioma, albeit not desmoplastic, in the introduction.We fully agree that the ability of mesothelioma to spread hematogenously is underestimated both in the literature and in clinical practice. Postmortem studies are sparse, the largest and most recent postmortem study (n=318) found extrathoracic metastases in 55.4% and central nervous metastases in 3% of mesothelioma patients (1). In living patients, only one retrospective cohort study (n=165) addressed this issue. Distant metastases were reported in up to 27% of all mesothelioma patients, depending on the affected organ site (2). One report (n=27) suggests that desmoplastic mesothelioma tend to metastasize more frequently than non-desmoplastic mesothelioma (3).
Background and purpose
Antiganglioside antibodies have been implicated in several autoimmune‐mediated neuropathies, and binding of these antibodies can result in inflammatory changes of the nerves. Diaphragmatic paralysis is a rare condition, mostly arising from diseases affecting the phrenic nerve, neuromuscular junction, or skeletal muscle.
Objectives
In this case series, we identified five patients with diaphragmatic paralysis due to unilateral or bilateral neuropathy of the phrenic nerve associated with the presence of antiganglioside antibodies (immunoglobulin G anti‐GT1a antibodies and immunoglobulin M anti‐GM1 antibodies).
Discussion
The combination of an isolated phrenic nerve palsy with anti‐GM1 antibodies has only once been described. On the other hand, the association of anti‐GT1a antibodies with phrenic nerve palsy has never been reported before.
Conclusions
We report an association between phrenic nerve palsy and the presence of antiganglioside antibodies, but it remains unclear if there is a causal relationship. Further studies are needed to explore this matter.
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