PSP current nomenclature and types

"The postmortem room has become the temple of truth" (Donald Calne, re PSP) (Neurology 2008)

Current nomenclature "Richardson disease" corresponds with initial descriptions. There is a gradual onset of postural instability and falls within the first two years, with vertical supranuclear gaze palsy, a frontal dysexecutive syndrome, rigidity and bradykinesia that is not responsive to leveodopa, and a life expectancy of six years.

A second milder group at pm (post-mortem) have PSP tau pathology that is more restricted and less severe are called PSP-P (PSP-parkinsonism). They have assymmetric bradykinesia of the limbs, an initial response to levodopa, tremor and limb dystonia without early falls, eye movement problems, or cognitive dysfunction. Most patients with "atypical PSP" are in this category.

The third rarer category is pure akinesia with gait freezing (PAGF). There is gradual onset of unsteady or slow gait and hypophonia progressing to gair freezing and start hesitation, without limb rigidity or tremor. There is no response to levodopa and there is no dementia or opthalmoplegia in the first five years. In types 2 and 3 the median duration of the disease is around ten years.

Other patients with similar tau-PSP pathology present with corticobasal ganglionic degeneration, progressive nonfluent aphasia, or apraxia of speech.

Practice pearl:  pay attention to SPEED of vertical saccades

 References up to date: Williams DR, de Silva R, Pavour DC et al. Characteristics of two distinct clinical phenotypes in pathologically proven progressive supranuclear palsy: Richardson' syndrome and PSP - parkinsonism. Brain 2005; 128:1247-1258. Williams DR, Holton JL, Strand C. et al. Pathological tau burden and distribution distinguishes progressive supranuclear palsy-parkinsonism from Richardson's syndrome. Brain 2007; 130: 1566-1576. Mizusawa H, Mochizuki A , Ohkoshi N, et al. Progressive supranuclear palsy presenting with pure akinesia. Adv Neurol 1993; 60: 618-621. Josephs KA, Duffy JR, Strand EA et al. Clinicopathological and imaging correlates of progressive aphasia and apraxia of speech. Brain 2006; 129: April 13. Tsuboi Y, Josephs KA, Boeve BF et al. Increased tau burden in the cortices of progressive supranuclear palsy presenting with corticobasal syndrome. Mov Disord 2005; 20: 982-988.
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Horners syndrome pearls

Note-skipping standard textbook items, this is a(my) blog and I am ONLY including minutiae that I want to remember later and am purposely omitting much common information about horner's that is already well known to me. This post is based on H Wilhelm, "The Pupil" Curr Opin Neurol 21:36-42 2008.

1. Many cases of Horners after evaluation remain idiopathic.
2. Iatrogenic Horners after subclavian/jugular venous puncture is fairly common and well reported
3. Carotid dissection is associated with 25 or 37 % Horners s., and the key clinical pearl is the association of PAIN and acuity. 15 % have a bad outcome so beware of this diagnosis.
4. Beware of VI paresis and Horners which usually localizes to cavernous sinus and indicates a mass lesion there.
5. Previously unknown mediastinal tumors are RARE. Only two percent of bronchogenic tumors are Pancoast tumors . Other tumors that RARELY present are thyroid (usually benign goiter but could be CA) and nasopharyngeal CA.
6. In children neuroblastoma is fairly common and needs to be ruled out. rhabdomyosarcomas and gangliogliomas also are reported in this population.
7. Cocaine testing in texts is difficult to the trouble getting cocaine drops. Apraclonidine can be an effective substitute. Like cocaine, the pupil is only denervated in the third neuron in the arc and only such third neuron lesions dilate with apraclonidine. It does reverse anisocoria in such cases. The jury is truly not back in for apraclonidine. More studies are indicated.
8. To differentiate meiosis in Horners from physiologic anisocoria, check time to dilatation in darkness. Infrared video can be used if available. Normal pupils start to filate by .5-1 s and reach maximal dilatation by 5 s, whereas Horner pupils reach maximal dilatation by 10 seconds. Its only sensitive if repeated about four times; if only done once, it will most likely be false negative, if done four times, is 83 % sensitive.

More facts about Horner's
9. Reported after chest tube insertion
10. reported after cervical block/epidural
11. Klumpke's paralysis, goiter,MS sympathectomy, chiari, lateral medullary infarct,acute otitis, mandibular abscess, neuroblastoma,and cervical rib are other causes
12. Signs may include loss of ciliospinal reflex, heterochromia (iris)
13. In animals leashes if too tight can cause Horner's syndrome
14. Drugs are overlooked cause esp drugs that affect DA levels
14. Sweating pattern analyzed by Morris lee and Lim:
The distribution of sweating on the face was studied in 31 patients with Horner’s syndrome. In patients whose lesion was known to be distal to the bifurcation of the common carotid artery impairment of sweating was confined to the medial aspect of the forehead and side of the nose. In more proximal lesions loss of sweating involved the whole of one side of the face. Facial sweating was normal in 6 patients with avulsion injuries of the brachial plexus and in 2 patients with a lateral meduliary syndrome. These findings suggest that the pattern of sweating in Horner's syndrome may be useful in some patients in localizing the site of the lesion. (Brain, 1984)

Oculomotor syndromes PEARLS

cf Tilikete C, Pelisson D. Oculomotor syndromes of the brainstem and cerebellum. Curr Opin Neurol 21:22-28 2008

Head shaking nystagmus (hsn)- usually is a peripheral vestibular lesion. However it can occur in Wallenberg syndrome.

In central positional nystagmus, Dix Hallpike testing induces downbeat nystagmus(DBN). DBN also occurs in floccular disturbance and the gravity dependent component can be suppressed with 3,4 aminopyridine. Other oddball causes of DBN include West Nile virus encephalomyelitis, intrathecal morphine, a particular genetic syndrome of cerebellar ataxia, or another syndrome combining DBN with motor neuronopathy and cerebellar ataxia.

Abnormalities (hemorrhages etc.) conjunctiva-causes

1.Subconjunctival hemorrhages-- common in trauma, rare in SAH and severe HTN
2. Leptospirosis-- injection of conjunctiva plus meningitis and myopathy
3. Filarial migratory phase of loa-loa-- injection is seen
4. telangiectasia in conjunctiva seen in sickle cell disease and ataxia telangiectasia
5. Retroorbital tumors can produce injection
6. Renal failure can produce severe conjunctival injection

Hypertelorism-- list of causes

1. normal
2. congenital absent callosum
3. Aicardi's syndrome
4. Schapiro's syndrome ( hypothermia and other congenital defects)
5. Septo-optic dysplasia

More pearls of fundoscopic exam temporal pallor and atrophy

Pallor is noted in any process affecting maculopapillary bundle.  The disk is alabaster white and bound by a gray white cup.  Green light of the opthalmoscope shows the fibers as they enter the disk. 

 

Optic atrophy has seven major features:   1) pale aspirin-white disc.  2)  sharp margins  3) loss of lamina cribosa  4)  increased cup to disc ratio  5) decreased arterioles off disc (less than 14)  6)  small arteries and 7) gray pale retina. 

 

Swelling has seven features  1) Loss of disk margin, superior then inferior then temporal  Always blurred nasal margins  2)  Fat veins without pulsations   3)  Erythema off the disk  4)  loss of lamina cribosa, whole disc pushed forward  5)  Slit hemorrhages off disc margin  6)  engorged veins appear and disappear near macula   7)  Folds in retina spread towards the macula.  Last normal acuity.

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Neuroopthalmology testing-- bedside pearls

Riddoch's phenomenon-- patient won't see an object in a damaged field unless it is moved.

shading of a visual field-- if larger objects are seen in a damaged field where smaller objects are missed, , suggests defect is partly caused by edema or pressure phenomenon.

Bjerrum screen (tangent screen) enlarges central meridian to 30 degrees and is most helpful for measuring central scotomata and the blind spot.

Graying of vision (finger does not appear flesh colored) or red desaturation (eg. red pin ) is appreciated before a quantifiable field defect.

Notes bitemporal upper quadrantic defect suggests chiasmal compression from above, but bitemporal lower field defect suggests compression from below.

Arcuate defect- optic nerve lesion prechiasmatic.

Bitemporal scotomata-- early bitemporal field defect or consider bilateral optic nerve lesions eg in kids.


Fundoscopic exam
Venous pulsations are seen only in the middle and not the margins of the disk unless there is a large pulse pressure such as in aortic insufficiency. severe hyperthyroidism or arteriovenous fistula.

Miscellaneous findings include commotio retina, an intense light streak seen with acute head injury of Kohlmeyer-Degos disease (arteritis with atrophic skin lesions).

Hemorrhages from papilledema occur off the disk margin (slit hemorrhages) whereas those from venous occlusion occur in the central retina and macula.

Torsten's syndrome is a hemorrhage that moves with head position following a burst aneurysm, also called preretinal or subhyaloid hemorrhage. Often can identify side of hemorrhage based on.

Lupus patients may have "grains of rice" or cytoid bodies in peripheral retina.

Renal patients may have a macular star (edema outlining the nerve sheath layer).

Hollenhorst plaque or branch point occlusion of cholesterol emboli are larger than occluded vessel birefringent and yellow.

Platelet fibrin emboli from HIT are white and multiple.

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Schwartzmann 2 second mental status exam

The tests below are not thorough or well vetted, but they can be done easily at grand rounds, appear novel to the students, and are explained in Robert Schwartzman's book on the neurological examination.

 

He tests judgment ("What would you do if you found a letter addressed to someone else?); visual praxis (copy a hand posture after seeing it for two seconds); language/memory/frontal four part oral command, and frontal face hand test (touches patient's hand and own face and asks where am I touching you).

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Transient visual loss

see also the following behavioral neurology post http://behavioralneurologynotes.blogspot.com/2008/05/hallucinations-and-related-conditions.html

Consider: noninschemic
1. opthalmic surface disorders

a. tear film abnormalities-- visual blurring occurs many times a week often at the end of the day and under one environmental circumstance. Blinking and lubricating eye helps. Patients with blepharitis may be worse in the morning due to accumulated meibomian gland secretion overnight. With dry eyes causing epithelial breakdown, there may be foreign body sensation, pain or redness with a positive Schirmer's test. Patients with rosacea frequently have opthalmic involvement. Also PD.

2. Other ocular causes-- narrow angle glaucoma causes transient blurring with halos. Recurrent spontaneous anterior chamber hemorrhages is such patients needs to be differentiated from those occurring in juvenile xanthogranuloma, malpositioned lens with iris contact, and iris neovascularization.

Patients with corneal dysfunction have episodes of blurred vision that last for hours especially in the mornings, must examine during an episode. Episodes in patients with diabetes due to hyper or hypoglycemia occur.

Ischemic Causes
Causes-- 60 % are due to carotid stenosis/occlusion. Also called TMB, amaurosis fugax, or retinal tia. In usual cases , emboli from carotid are common but low flow also occurs when collaterals from the Circle of Willis and eca are compromised. In these cases symptoms may be inducible by change in position or eating, or when distal flow is inadequate such as chronic ocular ischemia or bright light amaurosis. The latter occurs with TMB after sunlight or looking at a white wall, in the setting of carotid occlusion and is a well known phenomenon.
Risk of stroke per annum is 2 % with 1 % risk of permanent visual loss, v. 5-8 % risk of stroke with hemispheric tia's.

Symptoms are abrupt onset, painless, lasts 1-5 minutes, darkening or fogging (not blurring) of visual field, altitudinal pattern (shade closing) of vision loss, and return of vision over minutes.

Vision loss may be altitudinal, peripheral, central or even vertical. A nasal field defect may suggest emboli due to lodging in temporal retinal circulation. Rarely, scintillating scotomas occur. Pain which is rare may suggest temporal arteritis.

Neuroopthalmic signs-- the most common are retinal emboli, including cholesterol (Hollenhorst) plaques which are refractile, metallic gold appearance and indicate carotid disease and platelet fibrin emboli which are creamy white grey longitudinal intravascular opacifications that fill the lumen, and indicate either carotid thrombosis or thrombosis with recent MI. Chronic severe carotid disease leads to chronic ocular ischemia including episcleral and conjunctival injection, corneal edema, and neovascular glaucoma. Venous stasis causes microaneurysms and blot hemorrhages. Unlike diabetes they are unilateral (ipsilateral to stenosis) and mid periphery instead of posterior pole. Rarely retinal calcific emboli occur in patients with cardiac valvular disease. They are grey white and ovoid and infarct the retina.

In papilledema, episodes of grey black and white vision lasting seconds may occur. Its fleeting and associated with changes in position. This also occurs in pseudopappilledema drusen or colobomas. Gaze evoked amaurosis suggests intraorbital lesion such as glioma, nerve sheath meningioma, or intraconal mass such as cavernous hemangioma. Vision deteriorates seconds after eccentric gaze and returns to normal with straight ahead gaze.

Vision loss lasting seconds
papilledema, IIH, optic disc drusen, optic nerve sheath meningioma (need MRI with contrast),
gaze evoked (orbital tumor suspect). Get T1 image in 3 planes to differentiate MRV clot from physiologic narrowing of vessel

Vision loss can occur due to ACA aneurysm due to leakage of blood into opthalmic sheath

Patterns of functional visual loss

taken from Liu Volpe and Galetta text p. 388
TOTAL BLINDNESS
1. General observation of functionally blind-- may move into and bump objects without falling and hurting themselves; may not look at examiner speaking to them as a truly blind person might do; may wear sunglasses or mimic Stevie Wonder or other famously blind people.

2. Pupils-- should be abnormal except in cortically blind. A patient with total blindness and intact pupillary reflexes is likely to be functional. A complaint of photophobia with orbicularis oculi contraction to bright light is incompatible with an ocular cause of blindness.

3. OKN's- response is involuntary, but can be blocked by looking away from or beyond stimulus, or by excessive convergence.

4. Proprioceptive tests are performed by truly blind but not by functional. For example, looking at one's hand, bringing the tips of the fingers together from a distance, or signing one's name are better done by truly blind.

5. Mirror test-- a large mirror in front of a blind person, rocked, will produce an involuntary response if the patient is sighted and has better than hand motion vision..

6. Surprise-- atypical behaviors such as making faces, writing shocking words.

7. Evoked potentials-- a normal test can help, but an abnormal test can be ambiguous. My have in evoked fields, have characteristic hemifield loss from patient looking down.

UNILATERAL VISION LOSS
1. RAPD
2. Stereopsis-- requires binocular vision-- Titmus test
3. Placement of green lens should prevent visualization of Ishihara color plates

SEE BOOK FOR MORE

IRIS Immune reconstitution syndrome in HIV

NEUROLOGY 2009;72:835-841

Patients with low CD4 counts initiating cART therapy who then bump their CD4 counts and lower viral counts are at risk. Patients may or may not have concurrent infection. Authors describe 7 patients, with Neuro IRIS.

Presentations include trouble walking, seizure, encephalopathy, and occurred in early phase-- first 2-3 weeks after initiation of therapy (early, due to memory cells) or delayed, after 4-6 weeks phase (due to proliferation of new T lymphocytes)/ Latter tended to be a more prolonged course. Biopsy of one patient showed lots of CD8 and CD40 cells stained positive. CSF showed pleocytosis, and MRI showed diffuse white matter changes with enhancement. Lamivudine was in all cases one of the therapies used. The overall risk was 0.9 % among patients starting cART, but 1.5% when stratified with those having low CD4 count to start (<200). This is much lower than the number of non neuro IRIS cases that have been considered to be as high as 15 % although these numbers may be high.

Pearls for Multiple System Atrophy

Neurologist July 2008 14L224-237 authors Bhidayasiri R, Ling H.

MSA encompasses sporadic OPCA (MSA-C) and SND (OPC-P) with predominant Parkinsonism and both types including dysautonomia. Tremor is common but not classic pill rolling tremor. Impotence in men and urge incontinence in women are nearly universal, postural hypotension occurs in 2/3 and syncopal episodes in 15 %. Stridor and respiratory insufficiency may be presenting signs. 29 % respond to levodopa AT SOME POINT.

Red flags suggestive of MSA include early severe autonomic dysfunction, spontaneous or L dopa induced orofacial dyskinesias, which may even resemble risus sardonica in tetanus. Pisa syndrome is a form of axial dystonia, and camptocormia is forward flexion of the trunk. These are not specific and may be seen in PD. Disproportionate anterocollis may occur at any point of the disease, although rare, and botox for this can worsen dysphagia; this is a red flag. So is minipolymyoclonus, which is postural or stimulus sensitive small amplitude nonrhythmic movements of a few fingers or the whole hand. Dysarthria may be diagnostic, with a quivering, croaky strained element "reminiscent of myoclonic speech." (cit Arch Neurol 1996 53:545-548). Nighttime stridor is helpful diagnostically but poor prognostically and may present as laryngeal paresis. Sleep apnea, the "cold hand sign" and emotional incontinence comprise the other red flags.

groupings of "red flags: show six categories  early instability, rapid progression, abnormal postures, bulbar dysfunction, respiratory dysfunction, emotional incontinence.  Presence of two or more categories had high sensitivity (84 % ) and specificity (98%). see Hughes et al.  JNNP 1992; 55:181-184.

Exclusion criteria also are important, including age under 30, positive family history of MSA (PD is "OK"), frank dementia at onset, and eye movement abnormalities suggestive of PSP or CBGD.

The Quinn criteria for possible, probable and definite MSA are reviewed. International Consensus Conference Criteria of the AAN are considered better. See NEJM 2004; 351:912-924 (Case Records of the MGH).

MRI signs include atrophy of the cerebellar vermis, ponsmiddle cerebellar peduncles and lower brainstem. Signal change in the pons may resemble a "hot cross bun" (Catholics may understand this). In MSA-P, patients may have putamenal atrophy, with slit like void signal (black reflecting gliosis) which is sensitive but not specific, but is sensitive and specific if coupled with hyperintense T2 signal in the putamen. For a PD/MSA algorithm, see Arch Neurol 2002; 59:835-842). Onuf's nucleus degenerates which accounts for bladder problems. Pathologic confirmation is made by finding of alpah synuclein positive GCI's composed of misfolded alpah synuclein.

Pearls for treatment include, use of levodopa in many, the benefits of paxil 90 in one trial for motor function, botox of submandibular glands for drooling, and into adductor muscles for stridor, with concerns as above for other uses of botox. PT/OT/ST/ gait training and assistive devices are useful. Treatment of dysautonomic can include, if needed, avoiding large meal, alcohol, straining, certain meds; elastic stockings, bed tilt up at night. Drugs used for orthostasis include florinef, midodrine, desmopressin, octeotride, and eryuthorpoeitin. NGB can be treated with intermittent catheterisation, anticholinergics if detrusor hyperreflexia exists, suprapubic vibration devices, alpha adrenergic receptor antagonists, but NOT surgery. Beware of sildafenil for impotence due to hypotension. Macrogol 3350 for chronic constipation is safe and effective, increasing water content of stools. CPAP, may be needed, tracheostomy may be needed but also may be fatal due to hypercapnia. CPAP mat be contra-indicated if the epiglottis is floppy (Neurology 2011; 76:1841)

periictal water drinking localizes as does kissing epilepsy

Peri-ictal water drinking lateralizes seizure onset to the nondominant temporal lobe

E. Trinka, MD, G. Walser, MD, I. Unterberger, MD, G. Luef, MD, T. Benke, MD, L. Bartha, PhD, M. Ortler, MD and G. Bauer, MD

From the Universitätskliniken für Neurologie, Innsbruck (Drs. Trinka, Walser, Unterberger, Luef, Benke, Bartha, and Bauer), and Universitätsklinik für Neurochirurgie (Dr. Ortler), Innsbruck, Austria.

Address correspondence and reprint requests to Eugen Trinka, MD, Universitätsklinik für Neurologie, Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria; e-mail: eugen.trinka@uklibk.ac.at

The authors describe seven patients with medically refractory temporal lobe epilepsy whose seizures were associated with peri-ictal water drinking behavior. Presurgical evaluation, including video-EEG monitoring, MRI, SPECT, and neuropsychological testing, revealed a seizure onset in the nondominant temporal lobe. All patients had an excellent outcome after epilepsy surgery. Peri-ictal water  drinking may represent a lateralizing sign indicating seizure onset in the nondominant temporal lobe.

^{AAN 2010 PO5:210
Ictal kissing is a release phenomenon in nondominant temporal lobe epilepsy. 3 patients with ictal kissing were all righthanded women with longstanding right TLE.  Its occurrence to environmental cues suggests its a release phenomenon rather than an ictal event}

ictal eye closure = pseudoseizures

Ictal eye closure is a reliable indicator for psychogenic nonepileptic seizures

Steve S. Chung, MD, Paula Gerber, MD and Kristin A. Kirlin, PhD

From the Departments of Neurology (S.S.C., P.G.) and Clinical Neuropsychology (K.A.K.), Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ.

Address correspondence and reprint requests to Dr. Steve S. Chung, Department of Neurology, 500 West Thomas Road, Suite 300, Phoenix, AZ 85013; e-mail: sschung@chw.edu

Using data from video-EEG monitoring, the authors studied whether ictal eye closure was a reliable indicator of psychogenic nonepileptic seizures (PNES). Among the 52 patients with PNES, 50 consistently closed their eyes, while 152 of the 156 patients with epileptic seizures (ES) opened their eyes during seizures. These findings suggest that ictal eye closure is a highly reliable indicator for PNES, while ictal eye opening is an indicator of ES.

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Photic seizures

"Pokemon incident" showed alternating red and blue light each for 12 hz caused seizures in japanese kids. 1 seizure per 10000 kids watching (as opposed to 1-3 % photosensitive) but more have sensitivity to other stimuli. Most such kids had no knowledge they had prior seizures. More females by percentage but more males by number, more young, usually generalized but sometimes focal. Brightness, esp over 100 lux; flash rate over 5-30, must go on for more than a half second and fill at least half the field, colors red flashing are the worst (advise blue sunglasses); especially moving vertical bars (stripes), and viewer factors such as covering an eye, tired, meds, exposure time. More TV seizures in Europe because there is higher flicker rate in Europe.

Posterior reversible leukoencephalopathy s (PRES) PEARLS

First described at Tufts University Department of Neurology, 1996, by Judy Hinchey, Claudia Chaves et al.

1. Associations:
cytotoxic drugs (steroids, mtx, tacrolimus, cyclosporine, imuran)
hypertension
glomerulonephritis
porphyria
pheochromocytoma
malignant hypertension
eclampsia
NMO (neuromyelitis optica or NMO spectrum disorder)
autoimmune disease
sepsis
TTP
multiple organ dysfunction especially renal
2.  MRI pearls
--spares the calcarine cortex whereas stroke affects midline calcarine cortex
--may also affect frontal lobes, basal ganglia, brainstem, cerebellum
--no relationship between clinical severity, association, and location of lesions


3. treatment
remove drug
mag sulfate
control blood pressure

4 Review article Mayo Clin Proceedings May 2010 85:5: 427-432
120 cases in 113 patients over several years
-- may self resolve, but substantial Mortality and morbidity due to potential complications including massive infarction, hemorrhage, status epilepticus.
--hypertension present in 74 percent, but only 46 % of those had a history of chronic hypertension
--renal failure present in 57 %, but only half of those had chronic renal insufficiency
--clinical presentations included seizures in 74 % (partial or generalized, only rarely with history of seizures), 18 % with status epilepticus, 28 % with encephalopathy, 26 % with headaches, and 20 % with visual disturbances
-- Autoimmune disease was present in 45 %, of whom three fourths were women.These included TTP (27 %), SLE (18 %), hypothyroid (10 %), scleroderma (6%), Crohn's disease (6 %), ulcerative colitis or sclerosing cholangitis (4 %), RA (4%), DM ( 4%), and 1 patient each or 2 % for Graves' disease,  Hashimoto's thyroiditis, APL syndrome, anti glomerular basement disease, autoimmune hepatitis, polyarteritis nodosa, thromboangitis obliterans, polyglandular autoimmune syndrome, Sjogren's, gfrnulomatous interstitial nephritis, NMO
-- Of patients with autoimmune disease, 65 % had cerebellar involvement, and majority of septic patients had involvement of the cerebrum.
-- transplant and chemo and pediatric populations not represented in above article

Clinical Care of ALS patients

based on Radunovic Am Mitsumoto H, Leight PN Review article in Lancet Neurology October 2007. Based on the idea that basic medical management is underutilized. Major points:
1. Diagnosis (correct diagnosis) necessitates evaluation initially including brain and spine imaging (most of the time), CXR, lab tests, EMG. Use El Esocorial criteria http://www.wfnals.org/guidelines/1998elescorial/elescorial1998criteria.htm. Prior links to other important ALS information including EMG criteria, mimics and others. Dx is hardest with only UMN or only LMN signs. Mean survival is 30 months from diagnosis. Long survivors were not necessarily the ones taking riluzole. The ALS Functional Rating Scale http://www.outcomes-umassmed.org/als/alsscale.cfm and vital capacity are the most useful clinical measures.

Authors emphasize team approach and palliative care. Some of the treatments especially medicines are well known and obvious and are not reblogged. Some "tricks" are listed below.

excess saliva-- non medicine treatments include home suction, dark grape juice, sugar free citrus lozenges, nebulizers, botox, parotid radiation, steam inhalers. Medicines include elavil glycopyrrholate, hyoscine.

Excess broncial secretions-- propanolol, metoprolol, carbocysteine?, assisted cough insufflator/exsufflator. rehydration, pineapple or papaya juice, butter, decreased intake dairy products, alcohol and caffeine.

excess yawning-- baclofen

laryngospasm-- baclofen

emotional lability-- TCA's, Sinemet, dextromethrophan and quinidine

Noninvasive ventilation at onset of respiratory insufficiency among patients with no/moderate bulbar dysfunction improves survival. It also improves quality of life. Initiate when FVC is less than 40 % that of predicted and it doubles survival. Authors state measure of sniff nasal pressure is better than FVC and that measure of 32 % (= 25 cm H2O) or less predicts respiratory failure whereas FVC of 40-50 % does not do so as well . SNP less than 40 cm H20 predict survival. Other measures such as inspir/expir mouth pressures, PSM, sniff transdiaphragmatic pressureand diaph EMG provide more info. Begin noninvasive ventilation when patient has nocturnal hypoventilation including dyspnea and orthopnea. , low SNP, nocturnal desaturation (< 90 % for more than 5% of sleep) or AM hypercapnia more than 6.5 kPa.

Discuss tracheotomy with patient in advance. It prolongs life but is "beyond means" of many patients, who might not want it. Lorazepan, morphine are OK but not oxygen which (unless patient is hypoxic) worsens mouth dryness and hypercapnia.

Nutrition can be assessed with dietary history, BMI, and weight. Enteric feeding can be considered with more than ten percent weight loss. Swallow studies, assessment of choking, food texture, drooling, meal duration , fatigue, video studies to assess silent aspiration. Use thickeners, lip seal, tongue exercises, chin tuck flexing neck forward when swallowing) with eating smaller more frequent meals with enough calories.

Authors emphasize role of hospice, grief couselling for families.

new seizure drugs coming up

Drugs. 2008;68(14):1925-39.

Related Articles, Links

Pharmacological management of epilepsy : recent advances and future prospects.

Johannessen Landmark C, Johannessen SI.

Department of Pharmacy, Faculty of Health Sciences, Oslo University College, Oslo, Norway.

There is still a need for new antiepileptic drugs (AEDs) as the clinical efficacy, tolerability, toxicity or pharmacokinetic properties of existing AEDs may not be satisfactory. One new AED has recently been approved (rufinamide in 2007) and six others are in late-stage development (phase III and onwards) [brivaracetam, carisbamate, eslicarbazepine, lacosamide, retigabine and stiripentol]. The purpose of this review is to provide updated data on proposed mechanisms of action, efficacy and tolerability on these new AEDs, and to discuss the rationale for their development and possible advantages compared with existing treatment, based on recent publications and MEDLINE searches.Rufinamide, brivaracetam and stiripentol have been given the status of orphan drugs. Rufinamide was approved in Europe in 2007 for the use in Lennox-Gastaut syndrome. Brivaracetam has gained orphan status for development in progressive and symptomatic myoclonic seizures in Europe and the US, respectively. Stiripentol has gained orphan status in children with Dravet's syndrome and pharmaco-resistant epilepsy. All of these drugs demonstrate efficacy as adjunctive therapy in partial seizures. Three of the drugs are derivatives of existing AEDs: brivaracetam is a derivative of levetiracetam with improved affinity for the target molecule; carisbamate is a derivative of felbamate with improved tolerability; and eslicarbazepine is a derivative of carbamazepine with less interaction potential and no auto-induction. Lacosamide, retigabine, rufinamide and stiripentol are new compounds, unrelated to other AEDs.Further investigation and development of new broad-spectrum drugs is important for improved treatment of patients with epilepsy and other neurological and psychiatric disorders.

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Misc. Signs of drug use/withdrawal

1.  tachycardia
2.  hyperthermia
3.  purulent drainage from nares with erosions (think cocaine)
4.  pop marks on skin
5.  hear murmur/ other signs of SBE (see Harrison's textbook for list)

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Differential of delirium with quadriparesis/paraparesis

1.  central pontine myelinolysis
2.  progressive multifocal leukoencephalopathy
3.  acute disseminated encephalomyelitis
4.  Cobalamin deficiency (have not seen like this)
5.  cryptococcal meningitis
6.  critical illness neuromyopathy
7.  new onset myasthenia gravis, unsuspected, postoperative

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