Prominent Autonomic Features Research Articles

The epileptology of Koolen‐de Vries syndrome: Electro‐clinico‐radiologic findings in 31 patients

This study was designed to describe the spectrum of epilepsy phenotypes in Koolen-de Vries syndrome (KdVS), a genetic syndrome involving dysmorphic features, intellectual disability, hypotonia, and congenital malformations, that occurs secondary to 17q21.31 microdeletions and heterozygous mutations in KANSL1. We were invited to attend a large gathering of individuals with KdVS and their families. While there, we recruited individuals with KdVS and seizures, and performed thorough phenotyping. Additional subjects were included who approached us after the family support group brought attention to our research via social media. Inclusion criteria were genetic testing results demonstrating 17q21.31 deletion or KANSL1 mutation, and at least one seizure. Thirty-one individuals were studied, aged 2-35 years. Median age at seizure onset was 3.5 years, and 9 of 22 had refractory seizures 2 years after onset. Focal impaired awareness seizures were the most frequent seizure type occurring in 20 of 31, usually with prominent autonomic features. Twenty-one patients had prolonged seizures and, at times, refractory status epilepticus. Electroencephalography (EEG) showed focal/multifocal epileptiform discharges in 20 of 26. MRI studies of 13 patients were reviewed, and all had structural anomalies. Corpus callosum dysgenesis, abnormal hippocampi, and dilated ventricles were the most common, although periventricular nodular heterotopia, focal cortical dysplasia, abnormal sulcation, and brainstem and cerebellum abnormalities were also observed. One patient underwent epilepsy surgery for a lesion that proved to be an angiocentric glioma. The typical epilepsy phenotype of KdVS involves childhood-onset focal seizures that are prolonged and have prominent autonomic features. Multifocal epileptiform discharges are the typical EEG pattern. Structural brain abnormalities may be universal, including signs of abnormal neuroblast migration and abnormal axonal guidance. Epilepsy surgery should be undertaken with care given the widespread neuroanatomic abnormalities; however, tumors are a rare, yet important, occurrence.

Cluster headache in children and adolescents: Ten years of follow-up in three pediatric cases

Cluster headache (CH) is a rare cause of headache in children. Onset before 12 years of age is unusual, and long-term follow-up of pediatric cases has been not reported. To report three cases of CH with onset at childhood and at least ten years of follow-up. Case report. The first case is that of a 12-year-old boy with episodic CH with unilateral pain and striking, bilateral autonomic manifestations, remitted for over eight years. The second case is unique in that it reports a case of chronic CH in a 13-year-old boy with Down syndrome. The third case is that of a 9-year-old girl with episodic CH with remissions of 2 and 5 years. All cases had prominent autonomic features. The frequency and duration of the attacks were similar to those that have been reported in adults. Good response to indomethacin was obtained in two cases, although tolerability issues occurred in one. Sustained, long-term, medical and/or spontaneous remission occurs in CH of early onset. The phenotype and response to therapy in children, at least in these case examples, are similar to equivalent observations in adult patients with CH.

Panayiotopoulos Syndrome Presenting With Status Epilepticus and Cardiorespiratory Arrest

Panayiotopoulos syndrome is early-onset benign childhood epilepsy, now classified as an electroclinical syndrome. The original description in 1989 focused on the triad of nocturnal seizures, tonic eye deviation, and vomiting. With available data from the long-term studies, a wide variety of manifestations have been described, with recognition of autonomic features as being the most prominent aspect of this epilepsy. The presenting symptoms are usually focal seizures comprising autonomic symptoms and/or behavioral changes. Majority of these seizures are in sleep, with half of the seizures progressing to become secondarily generalized. Occasionally, these seizures can present with prominent autonomic features such as ictal vomiting, pallor, flushing/cyanosis, and tachycardia with prolonged thermoregulatory changes lasting for hours, constituting autonomic status epilepticus. Recovery from this autonomic status epilepticus is within hours and is always complete. Autonomic status epilepticus has been previously reported in this epilepsy syndrome, but ictal cardiorespiratory arrest is extremely rare, with only 4 cases being reported in literature. All 4 cases reported in literature recovered spontaneously and did not require resuscitation. Here we present a 3½-year-old male child with Panayiotopoulos syndrome who presented with status epilepticus and ictal cardiorespiratory arrest requiring cardiopulmonary resuscitation for revival.

Headaches and hyperhidrosis: clinical features and outcomes after surgery

Both headache disorders and hyperhidrosis are debilitating conditions. Several primary headache syndromes have prominent autonomic features; the main therapeutic option for severe, focal hyperhidrosis addresses the autonomic system (thoracoscopic sympathectomy). Accordingly, herein we assessed headache outcomes in patients with hyperidrosis after sympathectomy. Sample consisted of 53 patients (43 women and 10 men) with hyperhidrosis and headaches. Headache clinical features and outcomes were assessed at baseline and after surgery. Mean age of sample was 27.1 years; 29 patients had palmar-plantar hyperidrosis, 17 had palmar-axillary, 9 had craniofacial and 4 had purely axillary hyperhidrosis. Twenty four (54.8%) patients had migraine; 20 (37.7%) had probable migraine and 4 (7.5%) had tension-type headache. Headache onset occurred after hyperhidrosis onset in 37 (69.8%) patients. Anxiety was reported by 94% of patients. Twenty four (45.3%) patients reported improvement of headache symptoms aftersurgery, 23 (43.4%) reported no change and 6 (11.3%) had worsening of symptoms after surgery. Overall headache frequency was significantly reduced after surgery, as contrasted to baseline. Hyperhidrosis may be comorbid to migraine, trough shared autonomic dysfunctions

IFRD1 Is a Candidate Gene for SMNA on Chromosome 7q22-q23

We have established strong linkage evidence that supports mapping autosomal-dominant sensory/motor neuropathy with ataxia (SMNA) to chromosome 7q22-q32. SMNA is a rare neurological disorder whose phenotype encompasses both the central and the peripheral nervous system. In order to identify a gene responsible for SMNA, we have undertaken a comprehensive genomic evaluation of the region of linkage, including evaluation for repeat expansion and small deletions or duplications, capillary sequencing of candidate genes, and massively parallel sequencing of all coding exons. We excluded repeat expansion and small deletions or duplications as causative, and through microarray-based hybrid capture and massively parallel short-read sequencing, we identified a nonsynonymous variant in the human interferon-related developmental regulator gene 1 (IFRD1) as a disease-causing candidate. Sequence conservation, animal models, and protein structure evaluation support the involvement of IFRD1 in SMNA. Mutation analysis of IFRD1 in additional patients with similar phenotypes is needed for demonstration of causality and further evaluation of its importance in neurological diseases.

Defining neuralgiform headache with ipsilateral autonomic symptoms: case report in a headache center

Patients who fulfill the diagnostic criteria for primary headaches of the IHS Classification of Headache Disorders (2nd edn [1]) often consult an internal medicine specialist [2]. Headache is a common complaint in the general population. The 1-year prevalence of tension-type headache in men is 30–60% and in women 35–85% while the corresponding prevalence for migraine approximates 5% in men and 15% in women [3–5]. In addition to migraine and tension-type headache the IHS classification comprises a group called Trigeminal Autonomic Cephalalgias (TACs) including cluster headache, paroxysmal hemicrania and Short lasting Unilateral Neuralgiform headache with Conjunctival injection and Tearing (SUNCT). Clinically, they share halfsided head pain with prominent autonomic features. Particularly, SUNCT is very rare [6], sometimes can coexist with trigeminal neuralgia [7] and generally the differentiation between these two syndromes, which require specific treatment, is difficult. Diagnostic criteria for SUNCT are: (a) at least 20 attacks fulfilling criteria b–d, (b) attacks of unilateral orbital, supraorbital or temporal stabbing or pulsating pain lasting 5–240 s, (c) pain is accompanied by ipsilateral conjunctival injection and lacrimation, (d) Attacks occur with a frequency from 3 to 200 per day, (e) not attributed to another disorder. We present the case of a 65 year-old male admitted to our Headache Centre with a 8-year history of headache phases characterized by severe strictly left-side pain involving the eye, and nose with some extension to upper jaw. The patient’s past medical history indicated only arterial hypertension that had commenced ten years prior that was well controlled with drug therapy (association of delapril 30 mg and indapamide 2.5 mg/day). There was no family history of migraine or other headache syndromes. When he was 59 years old, the first period of headache attacks appeared. The pain was excruciating with a stabbing quality but not throbbing, and was associated with ipsilateral prominent conjunctival injection, tearing and nasal obstruction The attacks lasted from 1 to 10 s with absence of pain between attacks. The frequency of the crisis was 20–100 a day, and some attacks were triggered by speaking, swallowing, chewing. The pain remitted for variable periods. At the time of our observation, general and neurological examinations were normal. Routine blood tests and urinalysis were unremarkable. This included thyroid stimulating hormone, free thyroxine, adrenocorticotrophic hormone, testosterone, prolactin at 0 and 30 min, growth hormone (because of some case reports where SUNCT was associated with pituitary microadenomas [8–10]). MRI of brain revealed bilaterally multiple, ischemic areas in the white matter, no alterations of pituitary gland and the MRI of the cerebral district showed any alterations. The patient experienced four active periods of headaches between 59 and 62 years of age, which lasted from 10 to 15 days with the same symptoms. Before coming under our care, in his long lasting evolution the patient had been treated with different symptomatic medications e.g. ketorolac sublingual 30 mg, and tramadole 15 mg three times a day and prophylactic drugs without significant improvement. Carbamazepine had little effect and was abandoned because of side effects (particularly constipation); oral pregabalin (75 mg two times a day) and gabapentin (400 mg two times a day), not given in F. De Cesaris (&) M. Fanciullacci U. Pietrini B. Anselmi E. Del Bene Headache Center, Department of Internal Medicine, University of Florence, Villa Monna Tessa, Viale Pieraccini, 18, 50139 Florence, Italy e-mail: f.decesaris@dmi.unifi.it

Adult–onset seizure disorder in the 18q deletion syndrome

Sirs: Deletion of the long arm of chromosome 18, the 18q deletion or 18q-syndrome (also known as de Grouchy syndrome; OMIM#601808) produces a variable phenotype encompassing learning disability, short stature, variable dysmorphism (microcephaly, mid-facial hypoplasia, prominent antihelix, long tapering fingers) and neurological symptoms and signs (hypotonia, incoordination) [2, 6, 13, 14]. Magnetic resonance brain imaging (MRI) shows white matter abnormalities with incomplete myelination and poor differentiation of grey and white matter [3, 5], ascribed to loss of the myelin basic protein (MBP) gene which lies on 18q, since deletions in which the MBP gene is retained have normal appearing white matter [3, 5]. The condition has been classified with the leukodystrophies [1]. Neuropathological studies have shown, in addition to white matter changes, glial neuronal heterotopias and misplaced neurons in the molecular layer of the cortex, indicating cortical dysgenesis [8, 12]. Nonetheless, seizure disorders have only rarely been described in 18q-syndrome [4, 9–11], mostly in those of childhood onset. As this condition may be unfamiliar to neurologists working with adult patients, we report a patient with 18qsyndrome with complex partial seizures of adult onset. A 29-year-old woman with severe learning disability due to the chromosome 18q deletion was referred with a one-year history of blank spells. Her parents and carers had noticed stereotyped attacks in which she was pale, her head fell back, her eyes rolled or failed to make eye contact, associated with teeth grinding, moaning, slobbering, and sometimes jerking of the right arm. Episodes would last from 30 seconds to 2 minutes, and clustering of attacks was noted. Afterwards she was tired and would sleep for up to two hours. At best, she could go two weeks without the attacks. Her learning disability had been associated with behavioural disorders, specifically autistic behaviours and impulsive aggression. These had been briefly treated with carbamazepine but without benefit and the drug was stopped two years before the onset of the attacks. Only limited neurological examination was possible, showing mild muscular hypotonia, ataxic gait and eversion of the feet. The clinical history was suggestive of complex partial seizures. Only a limited standard EEG was possible, which showed generally low amplitude with excessive diffuse fast activity but no focal epileptic discharges. Photic stimulation had to be abandoned because of patient restlessness although some following response was seen. Hyperventilation was not possible. It was not thought justified to submit the patient to general anaesthesia for the purpose of MRI of the brain.An empirical trial of lamotrigine was given. This was associated with a reduction in the number of attacks, such that she could go several weeks without, and less drowsiness.Although her attacks may have been behavioural in origin, seizures are more likely given both the postictal phenomena and the response to lamotrigine. Although one review of the neurological manifestations of 18q-syndrome stated that “a substantial minority of patients have epilepsy” [6], we have identified few published reports [4, 9–11]. This is in keeping with a review of over 400 different chromosomal imbalances associated with seizures or EEG abnormalities which reported that “seizures have not been well-described in 18q syndrome” [7]. Most reports refer to seizures of childhood onset [4, 9, 11]. Seizure semiology has been variable, including complex partial seizures with prominent autonomic features [9, 10], apnoeic seizures [4, 9], and benign focal seizures [11]. Given the paucity of previous reports, it remains possible that seizures in patients with the 18qsyndrome represent a chance concurrence. It is not known what percentage of learning disabled adults and children with seizures have 18q-syndrome. However, since 18qmay be associated with neuronal migration disorders, seizures may be symptomatic in these cases. The possibility that dysmyelination contributes to epileptogenesis has been suggested [12] but seems less likely, given the near universality of white matter changes in 18qand the paucity of reports of seizures.

Rare primary headaches: clinical insights

So-called "rare" headaches, whose prevalence rate is lower than 1% or is not known at all and have been reported in only a few dozen cases to date, constitute a very heterogeneous group. Those that are best characterised from the clinical point of view can be classified into forms with prominent autonomic features and forms with sparse or no autonomic features. Among the former are trigeminal autonomic cephalalgias (TACs) and hemicrania continua, while the latter comprise classical trigeminal neuralgia, hypnic headache, primary thunderclap headache, and exploding head syndrome. The major clinical discriminating factor for the differential diagnosis of TACs is the relationship between duration and frequency of attacks: the forms in which pain is shorter lived are those with the higher frequency of daily attacks. Other aspects to be considered are the time pattern of symptoms, intensity and timing of attacks, the patient's behaviour during the attacks, the presence of any triggering factors and of the refractory period after an induced attack, and response to therapy, especially with indomethacin. Often these are little known clinical entities, which are not easily detected in clinical practice. For some of them, e. g., thunderclap headache, it is always necessary to perform instrumental tests to exclude the presence of underlying organic diseases.

Urinary dysfunction and orthostatic hypotension in multiple system atrophy: which is the more common and earlier manifestation?

OBJECTIVESUrinary dysfunction and orthostatic hypotension are the prominent autonomic features in multiple system atrophy (MSA). A detailed questionnaire was given and autonomic function tests were performed in 121 patients with...

The natural history of peripheral neuropathy in primary systemic amyloidosis

The records of 31 patients with primary systemic amyloidosis and peripheral neuropathy seen during a 17-year period were analyzed to define the natural history of the neuropathy. Patients tended to be older men with a painful, distal, symmetrical sensorimotor neuropathy and prominent autonomic features. Loss of pain and temperature sensation was frequently more striking than loss of mechanoreception. Renal, cardiac, hematological, and gastrointestinal dysfunction often overshadowed the neuropathy. Clinical, neurophysiological, and histopathological studies pointed to axonal degeneration with predominant but not exclusive involvement of small myelinated and unmyelinated fibers. The neuropathy was progressive in all patients with or without treatment, but death was typically due to supervening medical complications.