Persistent genital arousal syndrome: neurology of and comparison to epileptic orgasms

This post details  a  neurologic basis  to persistent genital arousal syndrome (PGAS).  The condition is characterised by unwanted repeated multiple daily episodes of sexual arousal, that often leads to dozens or hundreds of orgasms daily, relieved with masturbation briefly before recurring.  It can be lifelong, occur during pregnancy, or in the postmenopausal state.  Precipitating factors include pudendal nerve injury,  and antidepressant drugs including trazodone.  A strong association with restless legs syndrome and overactive bladder has been noted. Treatments that were successful in many patients include clonazepam, tramadol, pelvic floor massage focusing on the pudendal nerve, varenicycline,and pudendal nerve blocks.

This condition can be differentiated from orgasmic seizures, which itself needs to be divided into different entities.  Orgasms as an aura of a seizure can occur usually due to right hippocampal, but occassionally left hippocampal or left parietal epilepsy.  Reflex epilepsy after orgasm also occurs again usually after right temporal but occassionally left frontal seizures and in one case report reflected the manifestations of complete heart block, cured with a pacemaker.  Reflex epilepsy occurring as orgasmic aura has been reported after toothbrushing in one Taiwanese patient.

see pub med for references

Antiepileptic drugs and peripheral neuropathy

Effects of the antiepileptic drugs on peripheral nerve function; Boylu E, Domaç FM, Misirli H, Senol MG, Saraçoglu M; Acta Neurologica Scandinavica 121 (1), 7-10 (Jan 2010)

 

Upshot-- carbamazepine, but not valproate, oxcarbazepine and topirimate, affect nerve conduction studies among chronic takers.

Clinical pearls in diagnosis of vestibular disorders

1.  Look for nystagmus with and without fixation.  To achieve latter, either examine in a darkened room with Frenzel glasses or use opthalmoscope in one eye and cover the other.

2.  Nystagmus can be assessed with holding eyes 30 degrees from midline in 4 positions (L-R-U-D) each for 20 seconds.  Further out, and nystagmus is expected.  Use a chart to score.

3.  Nystagmus through eyelids can be confused with lid twitch.

4.  Features of central nystagmus that differ from peripheral include pure vertical, horizontal or rotatory rather than combined;  no effect of fixation;  may change direction;  central abnormality may affect pursuit or OKN. In central nystagmus, there may be a null zone near center after which nystagmus changes direction when eyes look in opposite direction.

5.  Head thust sign is a simple test at bedside, of horizontal component.  Move head rapidly a short distance horizontally in one direction and then other.  Eyes should at start be ten degrees from primary position so that after the thrust they will be near primary position.  Patient fixates on examiner's nose.  If there is a catch up saccade in one direction but not the other, that is evidence of a peripheral lesion on that side. The absence of a head thrust sign suggests a central etiology.

6.  Patients with peripheral lesions veer towards the side of the lesion when up.  Patients with central lesions often cannot stand.  Patients with central lesions are more likely to have dysarthria,  numbness or weakness.

7.  Viral labyrinthitis needs to be diagnosed after ruling out other entities.  Bacterial usually has associated mastoiditis that is identified on CT scans of the temporal bone.  Usually auditory and vestibular function both are affected with bacterial infection.

8.  Recurrent episodes that become bilateral and lead to deafness within months are associated with syphilis.

9.  Perilymh fistula often presents abruptly after a precipitating event, such as head trauma, barotrauma, strain while lifting, or sneezing.  It is very common among patients who have undergone stapedectomy for otosclerosis.  Patients with fluctuating symptoms or positive fistula test need to undergo surgery.

10. Very important: the Dix Hallpike test can be positive in central vertigo cases, including tumors, but features are different.  Central variety fails to attenuate with repeated tests, may last longer than 30 seconds, and may have fast phase downward to cheek (as opposed to peripheral which is to bottom ear and forehead). 

Classical Babinski-like signs

Extensor toe signs
Babinski response- extension of big toe, fanning of small toes with stroking plantar surface
Chaddock response- same response except stimulation is of lateral foot from lateral malleolus
Gordon leg sign-- same with stimulation of squeezing leg muscle
Oppenheim's sign-- same result with downward stroking of tibia and tibialis anterior muscle
Gonda's reflex--upward movement of big toe by moving another toe down and releasing with snap
Shaefer's sign-- Babinski response by squeezing Achilles' reflex


Non extensor toe  long tract signs
Rossolimo's sign-- same response with striking or tapping the ball of the foot
Mendel-Bechterew sign- flexion of 4 outer toes by striking dorsum of foot
Hoffman's sign-- Clawing of the thumb and all fingers by flicking distal phalanx of index finger
Gordon's finger sign-- flexion of fingers or thumb/index finger with pressure over pisiform bone
Chaddock's wrist sign- wrist flexion, extension & fanning of fingers with stimulation of ulnar side of hand
Hirschberg's sign- adduction and internal rotation while stroking the inner border of foot
Ankle clonus-- may be normal if unsustained
Patellar clonus (trepidation sign)-- lifting relaxed knee suddenly looking for increased tone

Other pathologic signs
Beevor's sign-- with lesion at T10, the patient tenses abdominal muscles and ombilicus moves upwa rds, doe to paralyzed
Mass reflex of Riddoch-sudden emptying of bowel and bladder, flexion of lower limbs and sweating.  Its released pathologically by severing spinal cord and striking skin below

Classical abnormal gaits

Tabetic (ataxic) gait
Hemiplegic gait
Steppage gait
Scissors gait
Drunken or ataxic gait
Waddling or clumsy gait
Festinating gait
Hysterical gait
astasia - abasia

metoprolol : no effect on QOL in recurrent syncope

Effect of metoprolol on quality of life in the prevention of syncope trial; Sheldon RS, Amuah JE, Connolly SJ, Rose S, Morillo CA, Talajic M, Kus T, Fouad-Tarazi F, Klingenheben T, Krahn AD, Koshman ML, Ritchie D; Journal of Cardiovascular Electrophysiology 20 (10), 1083-8 (Oct 2009)

INTRODUCTION: Vasovagal syncope is common, often recurrent, and reduces quality of life. No therapies have proven useful to improve quality of life in adequately designed randomized clinical trials. Beta-blockers have mixed evidence for effectiveness in preventing syncope. METHODS: The Prevention of Syncope Trial was a randomized, placebo-controlled, double-blind, multinational, clinical trial that tested the hypothesis that metoprolol improves quality of life in adult patients with vasovagal syncope in a 1-year observation period. Randomization was stratified in strata of patients<42 and>or =42 years old. The quality of life questionnaires Short Form-36 (SF-36) and Euroqol EQ-5D were completed at baseline and after 6 and 12 months of treatment by 204, 132, and 121 patients, respectively. RESULTS: There were 208 patients, mean age 42 +/- 18, of whom 134 (64%) were females. All had positive tilt tests. There was no improvement in quality of life during the trial in the entire group or in either treatment arm. Patients in the metoprolol treatment arm did not have improved quality of life compared to the patients in the placebo arm using either the SF-36 or EQ5D after either 6 or 12 months. Finally, there was no improvement in quality of life associated with metoprolol use in patients either<42 or>or =42 years of age. CONCLUSION: Metoprolol does not improve quality of life in patients with recurrent vasovagal syncope and a positive tilt test.

ED treatment of migraines: i-v prochlorperazine plus Benadryl beats sumatriptan

A Prospective, Randomized Trial of Intravenous Prochlorperazine Versus Subcutaneous Sumatriptan in Acute Migraine Therapy in the Emergency Department; Gutierrez FJ, Rieg TS, Moore TS, Gendron RT, Kostic MA; Annals of Emergency Medicine (Dec 2009)

STUDY OBJECTIVE: Intravenous (IV) prochlorperazine with diphenhydramine is superior to subcutaneous sumatriptan in the treatment of migraine patients presenting to the emergency department (ED). METHODS: In this randomized, double-blind, placebo-controlled trial, after providing written informed consent, patients presenting to the ED with a chief complaint of migraine received a 500-mL bolus of IV saline solution and either 10 mg prochlorperazine with 12.5 mg diphenhydramine IV plus saline solution placebo subcutaneously or saline solution placebo IV plus 6 mg sumatriptan subcutaneously. Pain intensity was assessed with 100-mm visual analog scales (visual analog scale at baseline and every 20 minutes for 80 minutes). The primary outcome was change in pain intensity from baseline to 80 minutes or time of ED discharge if subjects remained in the ED for fewer than 80 minutes after treatment. Sedation and nausea were assessed every 20 minutes with visual analog scale scales, and subjects were contacted within 72 hours to assess headache recurrence. RESULTS: Sixty-eight subjects entered the trial, with complete data for 66 subjects. Baseline pain scores were similar for the prochlorperazine/diphenhydramine and sumatriptan groups (76 versus 71 mm). Mean reductions in pain intensity at 80 minutes or time of ED discharge were 73 mm for the prochlorperazine/diphenhydramine group and 50 mm for those receiving sumatriptan (mean difference 23 mm; 95% confidence interval 11 to 36 mm). Sedation, nausea, and headache recurrence rates were similar. CONCLUSION: IV prochlorperazine with diphenhydramine is superior to subcutaneous sumatriptan in the treatment of migraine.

seroquel for refractory migrained pilot study

An Open Pilot Study Assessing the Benefits of Quetiapine for the Prevention of Migraine Refractory to the Combination of Atenolol, Nortriptyline, and Flunarizine; Krymchantowski AV, Jevoux C, Moreira PF; Pain Medicine (Dec 2009)

Background. Migraine is a prevalent neurological disorder. Although prevention is the core of treatment for most, some patients are refractory to standard therapies. Accordingly, the aim of this study was to evaluate the use of Quetiapine (QTP) in the preventive treatment of refractory migraine, defined as previous unresponsiveness to the combination of atenolol, nortriptyline, and flunarizine. Methods. Thirty-four consecutive patients (30 women and 4 men) with migraine (ICHD-II), fewer than 15 days of headache per month, and not overusing symptomatic medications were studied. All participants had failed to the combination of atenolol (60 mg/day), nortriptyline (25 mg/day), and flunarizine (3 mg/day). Failure was defined as<50% reduction in attack frequency after 10 weeks of treatment. After other medications were discontinued, QTP was initiated at a single daily dose of 25 mg, and then titrated to 75 mg. After 10 weeks, headache frequency, consumption of rescue medications, and adverse events were analyzed. Results. Twenty-nine patients completed the study. Three patients withdrew and two were lost to follow-up. Among those who completed, 22 (75.9%; 64.7% of the intention-to-treat population) had greater than 50% headache reduction. The mean frequency of migraine days decreased from 10.2 to 6.2 per month. Use of rescue medications decreased from 2.3 to 1.2 days/week. Adverse events were reported by nine (31%) patients. Conclusions. Although limited by the open design, this study provides pilot data to support the use of QTP in the preventive treatment of refractory migraine. Controlled studies are necessary to confirm these observations.

Kearn's Sayre syndrome

Rowland's diagnostic criteria

 

Obligate triad

1) Onset before 20

2) Progressive external opthalmoplegia

3) Pigmentary retinopathy

 

plus at least one of:  CSF protein>100, ataxia, cardiac conduction block

 

 

websites for genetic information

http://www.geneclinics.org/

http://www.neuromuscular.wustl.edu/

http://www.pdgene.org/

Neurotoxicology: sources of lead in adults

Lead poisoning occurs due to inhaling inorganic lead salts and fumes in processes involving remelting of lead. These include painting, printing, pottery glazing, lead smelting, welding and storage battery manufacturing. Other cases have occurred in miners, foundry and garage workers especially those who soldered radiators. Aruvedic herbal remedy for arthritis is described. Moonshine whiskey was very common in one series. The presentation is colic, anemia and peripheral neuropathy. It responds somewhat to calcium salts but not morphine (colic). Organic lead poisoning occurs in those who clean gasoline storage containers with insomnia, hallucinations, delusions and irritability. Hematologic changes are not found, and its usually reversible.

Stiff man syndrome (stiff person syndrome) Pearls

1. Insidious onset, then robotic appearance to walking and exaggerated lumbar lordosis in middle aged. Attempted passive movement causes a unique rock like immobility.

2. Trismus does not occur, and eye movements are not affected. Noise may precipitate an attack. Reflexes are normal, and lumbar spine is stiff on exam.

3. "Stiff limb" in one leg, spreading to other, has same antibodies (anti GAD) is similar to lcoalized tetanus.

4. EMG is normal and spasms disappear during sleep and anesthesia, differentiating from myokymia and Isaac's syndrome.

5. Rare paraneoplastic form usually accompanies breast cancer with antibodies to amphiphysin or gephyrin (proteins related to synaptic GABA receptors) and may be accompanied by opsoclonus or encephalopathy.

6. Differential diagnosis includes tetanus, Isaac's syndrome and myoclonic spinal neuronitis.

7. An infantile form starts at age 2 months and disappears by age 2.

Lysosomal storage diseases in adults

1. Of 45 or so diseases, all are autosomal recessive except the 3 that are X linked, namely Hunter's disease (mucopolysaccharadosis type II), Fabry's, and X linked myopathy with cardiomyopathy (lysosomal associated membrane protein 2, or LAMP 2).

2. GM2 can resemble Friedrich's ataxia, but unlike Friedrich's has hyperreflexia, episodic psychosis, and absent cardiomyopathy and scoliosis which should give away the diagnosis.

3. Dementia is common, and is a presenting feature of Kuf's disease type M and adult onset MLD. Dementia is most common presenting feature of adult onset mannosidosis, fucosidosis, aspartylglucosaminuria, Niemann Pick type c (along with vertical gaze palsy, dystonia, and dysarthria)

4. Progressive myoclonic epilepsy occurs in Kufs disease type A with spike wave on EEG and photosensitivity at low flash frequencies (see Berkovic 1988 Brain for review article).  Type B is characterized by dementia, ataxia,  EPS and facial dyskinesias.  Sialodosis type I aka cherry red spot myoclonus has treatment resistant epilepsy with macular cherry red spot and abnormal neuraminidase in skin fibroblasts.

5.  Late onset myopathy occurs in Pompe's disease, with high CPK, accumulated glycogen in vesicles, and deficient alpha glucosidase which is hard to measure.  Danon disease is X linked recessive and has hypertrophic cardiomyopathy and muscle weakness, and muscle biopsy shows autophagic vacuoles with glycogen. Its due to LAMP 2 deficiency.  There is mild MR and usually, death before 30. 

Managing adults with hydrocephalus : pearls

This post assumes patients who received a shunt as a child has problems as an adult

1. Signs of shunt malfunction/ increased ICP. On PE look for VI n palsy, papilledema, +/- reliability of shunt pump test

2. On history consider HA worse in AM or with recumbency, associated vomiting with relief, and diplopia suggest raised intracranial pressure. If HA is worse when up, consider low pressure headache

3. On imaging, assess all 4 ventricles independently, look for periventricular edema, edema around proximal shunt tip, loss of cerebral sulcal pattern near vertex, or loss of CSF spaces in basal cistern and Sylvian fissure. ALWAYS compare to prior scan closely.

4. ETV or endoscopic third ventriculostomy is used in some patients especially with third ventricular obstructions. ETV has a risk of catastrophe, a higher risk of immediate failure, a lower risk of long term failure but still can obstruct years later (unlike most standard shunts). ETV has the compelling advantage of a lower infection risk.

5. Patients with myelomeningocoele should be evaluated in a top down manner: shunt obstruction, Chiari malformation, syringomyelia/syringobulbia, and tethered cord. Often neurosurgeons will want to surgically manage the shunt to make sure it is working before embarking on other issues in these cases. An example case in Continuum was a patient who had presented with hand weakness and syringomyelia, but who had massively dilated ventricles and whose primary problem was in fact the shunt dysfunction.

Fragile X tremor ataxia syndrome (FXTAS)

FXTAS is due to premutation, and an excess amount of FRMP protein (50-200 repeats). Not all carriers develop FXTAS. Features include

1. usually presents with intention or action tremor with handwriting or using utensils

2. above is followed by ataxia with falls and unstable gait
above occurs in male carriers at a rate of 17% by 50's, 38 % by 60's, 47 % by 70's and 75 % by 80's. Women have less FXTAS with 8 % of those with premutation affected.

Other neurologic features
1. painful neuropathy

2. autonomic dusfunction (erectile dysfunction, hypertension, OH, urinary urgency and frequency, and incontinence.  Girls develop premature ovarian insufficiency or POI. 

3. White matter abnormalities (increased T2 intensity)especially bilateral cerebellar peduncles but elsewhere in deep white matter(seen in 60 % males, 13 % of females)

4. Executive dysfunction, short term memory loss, disinhibition and dementia

5. Unique eosinophilic intranuclear inclusions in neurons and astrocytes especially in the hippocampus and in the limbic system that are tau negative. They also occur in the PNS including the pericardiac and mesenteric ganglia and Leydig cells of testes.

6. Testosterone deficiency

7. Anxiety, social phobia and depression

8. Women with FXTAS : 43 % have fibromyalgia and 50 % have thyroid disease usually hypothyroidism

9. 2-3 per 100 develop multiple sclerosis and some develop Alzheimers

Treatment: SSRI's for anxiety, lithium for depression

Fragile X syndrome (FXS) clinical features

1. long face
2. prominent long ear pinnae
3. high arched palate
4. mitral valve prolapse
5. dilated aortic arch
6. flat feet
7. hyperextensible finger joints in childhood
8. macroorchidism (testicular volume greater than 30 cc in adulthood)
9. soft or velvet like skin.
10. Daughters can receive premutation only, sons cannot receive gene from their father
11. Single palmar crease

rare problems-- elasticity leads to increased hernias, and dilation of ureteric root leads to hydronephrosis.

Neuropsych
1. hyperarousal to stimuli with increased sympathetic response
2. Agression, anxiety
3. Concrete thinking
4. Dramatic decline of cognition in middle or later life, due to FRMP regulating amyloid precursor protein (APP) leading to coexisting Alzheimer's disease
5. Men typically are not sexually active and do not marry (not invariable)