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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Porphyria pearls

taken from NEJM CPC 2008; 358;2813-2825

case (abbreviated severely). 57 year old woman was admitted with abdominal pain and weakness. She had just had bariatric surgery for obesity. MRI showed changes of posterior reversible leuokoencephalopathy syndrome (turns out it occurs in porphyria). She had had intermittent dark urine and tachycardia.

Patient developed numbness, weakness and tingling in lower extremities, fell while walking and had an episode of confusion and urinary incontinence. She quickly (within days) could not stand or sit independently, became incontinent of stool with numbness and tingling along her body. She had 4/5 strength throughout, with fatigueing and absent reflexes. Sensation was normal. CSF showed normal glucose, protein and no cells. EMG showed an acute motor neuropathy. Strength deteriorated to 0-3/5, worse in proximal than distal legs. There was no response to IVIG.

Pearls-- factors for porphyria in this case were recurrent severe abdominal pain, dark or reddish urine, arterial hypertension, tachycardia and constipation. The diagnostic test in 5-ALA and PBG in urine or serum. A rapid test is the PBG in urine (Hoesch or Watson-Schwartz reaction). Key is diagnose porphyria first then type it. (False positives in 5-ALA are lead posioning and hereditary tyrosinemia type I).

Most types are inherited but the most common type, porphyria cutanea tarda is acquired, associated with liver disease and iron overload. Of 4 types, any may present with neurovisceral presentation esp colicky abdominal pain, and hereditary coproporphyria and variegate porphyria can also present with cutaneous features. Attacks are likely precipitated by adverse effects of excess ALA which is structurally similar to GABA. Starvation, poor CH2O/ energy intake, drugs, alcohol, smoking, infections and stress can ppt. In this case the negative energy balance with surgery caused up regulation of hepatic ALA synthase 1, due to loss of CH2O repression of rate controlling enzyme for heme synthesis in the liver. Other "bad " drugs in this case were phenytoin, tramadol and bactrim. Sulfonamides and barbiturates are also "bad." So is progesterone (which is why postpubertal women are more susceptible). The treatment is i-v heme. It can prevent reversible axonal death. Prognosis is slow and incomplete recovery. Noted also in this case wwre blisters in sun exposed parts of the body. She had variegate porphyria.

MoCa test for cognitive impairment

The MoCA test is an alternative to the MMSE which has had its share of problems.  Link for information  http://www.mocatest.org/

 

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Insulinoma mimicking seizure

Bazil CW, Pack A Insulinoma presenting as a seizure disorder. Neurology 2001; 56:817-818.

This rare disease mimicking a common disease needs to be added to the knowledge of doctors diagnosing individuals with various "spells." A 45 year old woman had troubel with panic attacks, inability to focus, tongue/limb tingling, perception of yellow spots and cold sweat. She later developed episodic unresponsiveness and jerking. Waxing and waning irda and polymorphic delta was seen on eeg, without interictal discharges, and the patient was felt to have pseudoseizures. A low glucose of 55 was found, islet cell tumors of the pancrease were found and removed and the patient took diazoxide with improvement.

Insulinoma usually includes nonspecific symptoms such as dizziness, apathy, headache and confusion. It is rare. affecting at most 5 per million.

Neuropsychiatric Profiles of Patients with Insulinomas; Ding Y, Wang S, Liu J, Yang Y, Liu Z, Li J, Zhang B, Chen Y, Ding M; European Neurology 63 (1), 48-51 (Dec 2009)
A review of 42 patients with insulinoma was undertaken, showing that many went undiagnosed for up to five years with neurologic and neuropsychiatric symptoms. 12 were misdiagnosed as epilepsy with eeg findings. Others received psychiatric diagnoses. Clinical presentation was usually confusion, convulsions and visual disturbance.

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manage carotid body tumor

fromClinical Neurology News:

Resection Remains Best Treatment for Carotid Body Tumors
PATRICE WENDLING (Chicago Bureau)
Article Outline
• Skip Angiography, and Other Surgical Pearls
• Copyright
CHICAGO — Surgical resection remains the treatment of choice for carotid body tumors, as presented in a review of 88 patients at one center.
Radiation therapy and chemotherapy are unsuitable alternatives because these rare tumors are too slow growing, and radiation exposes the carotid arteries to radiation arteritis, accelerated atherosclerosis, and even necrosis, Dr. Thomas A. Whitehill said at a vascular surgery symposium sponsored by Northwestern University.
Preoperative percutaneous tumor embolization has been tried with mixed results, but can be an important adjunct when treating select patients with large tumors (greater than 6 cm). There has been one report of a successful use of covered stents to facilitate resection (J. Vasc. Surg. 2003;38:389–91).
The malignancy rate for carotid body tumors is hard to define because there are no reliable histologic markers, but is thought to range from 2% to 5%, he said. Even if benign on histologic exam, all tumors, once discovered, should be surgically removed because they will ultimately wrap around the internal and external carotid arteries, erode into the base of the skull, and entrap neighboring cranial nerves. Increasing size also can interfere with speech, swallowing, and respiration, said Dr. Whitehill of the vascular surgery division of University of Colorado Health Science Center, Denver.
From 1993 to 2007, Dr. Whitehill and colleagues surgically resected 88 Shamblin classification II or III carotid body tumors, with an average diameter of 10.4 cm (range 5–16 cm). The patients ranged in age from 30 to 40 years.
Surgery time ranged from 4 to 14 hours, with an average blood loss of 375 mL (range 50–1800 mL). An internal carotid artery (ICA) resection bypass was performed in three patients, and ICA ligation in none.
Complications were relatively low, Dr. Whitehill said, and included cranial nerve IX neuropraxia (4%) or injury (1%), cranial nerve XII neuropraxia (30%), and superior laryngeal nerve injury (10%). There were no strokes or deaths.
Surgical advances and the widespread use of CT and MRI have decreased the overall risk of postoperative stroke over the past 25 years from about 30% to less than 2%, although the incidence of cranial nerve injury remains high at 15%–35%, he said.
Skip Angiography, and Other Surgical Pearls
Dr. Thomas A. Whitehill offered tips for carotid body tumors.
▸ Skip the angiography suite when making the diagnosis, and focus on CT imaging, preferably axial cuts rather than reconstructions. MRI may be slightly better at evaluating distant, metastatic deposits at the skull base.
▸ A nerve stimulator may be useful for preoperative identification of the cranial nerve.
▸ Do preoperative vocal cord and speech evaluations.
▸ Consider serial embolization in patients who are too old or have too many comorbidities to tolerate surgery.
▸ On a side CT view, draw a line between the mastoid tip and the angle of the mandible to get an idea of how high an exposure is needed and to help with preoperative planning.
▸ Utilize nasotracheal intubation in most patients, as it provides greater mobility with the mandible when resecting large tumors.
▸ In high access cases, mobilize the parotid gland anteriorly, up to the level of the facial nerve.
▸ Gain vascular control, if possible, and mobilize the tumor circumferentially to assess the extent of disease.
▸ Resect the tumor from proximal to distal.
▸ Fine mosquito clamp dissection and 3–0 or 4–0 silk ligation can give the best hemostasis.
▸ Send all suspicious lymph nodes for frozen permanent sections.
▸ Rather than using maxillomandibular arch bar fixation to obtain mandibular subluxation, consider interdental cross-wiring between the maxilla and mandible using bicuspids in dentate patients and Steinmann pins in patients with no teeth.
▸ For very distal tumors, cutting the digastric muscle will get you within 2 cm of the skull base.
▸ For large tumors, ligating the external carotid artery near its takeoff provides greater mobility.
▸ Avoid ligation of the internal carotid artery.
▸ If a tumor is 6 cm or more in diameter, consider preoperative embolization.
▸ Pushing the tumor completely through the bifurcation or pulling it anteriorly through the bifurcation may improve exposure angles and ease dissection.
▸ Take your time after the tumor is cleared of the two carotid arteries. The posterior surface and medial side of the tumor still must be separated from the deeper parapharyngeal tissues. Haste at this stage can result in the superior or inferior laryngeal nerves being transected or medial pharyngeal injuries, causing substantial swelling and neck pain in patients.

Typing PSP

"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. 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.

Limbic encephalitis : An expanding concept: teratomas and "things"

Graus F, Saiz A. Neurology 2008; 70: 500-501 (editorial) . Also see http://dementianotes.blogspot.com/2008/06/vgkc-autoantibodies-mimicking-cjd.html re VGKC antibodies in particular.

A syndrome of encephalitis in 12 women with teratomas of the ovary follows a predictable clinical pattern. A prodromal fever, is followed in a few days by a prominent psychiatric syndrome or short term memory loss, then, seizures, then progressive unresponsiveness (catatonia like stage) , dyskinesias, autonomic instability, and central hypoventilation. ICU support for weeks or longer may be necessary, and patients recover generally after tumor removal or immunotherapy (pheresis or IVIG). MRI is usually negative (9/12). All patients had CSF and serum antibodies against components of NMDA receptor (NMDAR) especially 2 subunits NR1/NR2). These particular patients express NR1, which is ubiquitously expressed in brain, but in these patients distributes with NR2 (basal forebrain) and disappears with treatment. This contrasts with NR2B which is seen in Rasmussen's excephalitis, refractory epilepsy, and stroke. In neuropsych lupus, this epitype leads to apoptosis.

Iizuka et al. now describe this epitype in Japanese juvenile non-herpetic encephalitis (with NMDAR). They emphasize the abnormal movements, especially orolingual after initial psychiatric syndrome and catatonic like state. These patients can reverse even after long periods of ventilator dependence.



Update  pearls for NMDAR  from Neurology 2014; 82: 550-551 (editorial)

1.  Tests for:  CSF with HEK cells expressing GluN1/2 subunuts of the NMDAR cell based assay. or serum.  with serum there is a 15 % false negative/positive result

2.  Adult men more often presented with seizures (18 %) whereas women more oftenpresent with behavior/psych symptoms  

3.  Among women, 41 % had tumors, all ovarian teratomas.  Among men only one had a tumor likely unrelated schwannoma. 

Rosai-Dorfman disease presenting with widespread intracranial and spinal involvement

Kidd DP, Revesa T, Miller NR. Neurology 2006; 67:1551-1555.
Disease is also known as sinus histiocytosis with masssive lymphadenopathy. It has a much more benign prognosis than histiocytosis X. A registry published in 1990 of 238 patients showed that of 238 patients, 49 had a lasting remission, 165 had stable disease not requiring treatment, and 21 had died 4 of the disease. It presents in the third to fifth decade with cervical lymphadenopathy often preceded by a viral infection, with elevated ESR and polyclonal gammopathy. Steroids and/or XRT is used for treatment. Authors present two neurologic cases. One mimicked a sellar meningioma with loss of vision, hearing and smell. A gallium scan and chest CT showed chest lesions. The other presented with four months of progressive visual loss. Only 4 % have neurologic involvement (8 patients) five with spinal dural based lesions, three with intracranial epidural lesions.

My question: cases did not describe cervical adenopathy so why was diagnosis made?

Unusual sources of lead leading to intoxication

Lead was an ingredient of antibacterial ointments until the 20th century and are still sold in rural Switzerland. Traditional remedies including Asian plant products may be contaminated. Beauty ointments may be a culprit including lip balms (Fluri et al. Neurology 69:929 2007).

Serum, not urine lead levels should be checked and porphoryns may be elevated. MRI may show hyperintensity in the basal ganglia. Encephalopathy and motor neuropathy both can occur in adult intoxications.

Bacterial and fungal meningitis in patients with cancer

Safdieh JE, Mead PA, Sepkowitz KA et al. Neurology 2008; 943-947. High points-- only five percent of cases had the triad of fever, nuchal rigidity and mental status changes. VP shunt patients usually presented with mental status changes. Most patients had had prior neurosurgery. organisms included more gram positive infections and a smattering of diverse other organisms. CSF response was often muted.

Differential diagnosis of cervical radiculopathy

1) Peripheral nerve entrapment (eg CTS)- see positive Phalen's and Tinel's sign, typical distribution, abnormal nerve conduction studies v. normal in cervical radiculopathy

2)Rotator cuff abnormal-- pain in shoulder or arm, rarely below elbow, worse with shoulder movements, normal sensation and reflexes.

3) Acute brachial plexitis-- (Parsonage Turner)-- see pain in neck shoulder and arm followed within days to weeks by weakness especially in C5-6 region as pain recedes (whereas in radiculopathy pain and weakness coincide).

4) Thoracic outlet syndrome-- Pain in shoulder and arm, intermittent paresthesia, C8-T1 symptoms (rare in radiculopathy), reproduction with provocative tests including Roo's test (rapid flexion and extension of fingers with arms abducted at 90 degrees and externally rotated 90 degrees), normal neuro exam, decreased radial pulse with vascular compression (rare) and usually normal NCS.

5) Herpes zoster-- neuropathic pain in dermatomal distribution followed by vesicular rash.

6) Pancoast syndrome-- Pain in shoulder/arm due to plexus compression, paresthesia is in C8-T1 distribution (intrinsic hand muscles), ipsilateral ptosis, miosis, and anhidrosis.

7) Sympathetic mediated syndromes-- pain and burning in arm with swelling, hyperesthesisa, allodynia, and vasomotor changes (temperature and color) with normal neurologic examination.

8) Referred somatic pain from neck-- such as discs, joints, usually segmental C5-6 felt in posterior neck and supraspinatus fossa, normal neuro exam.

9) SUNCT/SUNA syndromes with pain in cervical region

Cervical radiculopathy

Carette S, Phil M, Fehlings MG. Clinical practice. NEJM 2005; 353:392-399.

The etiology in 70-75% is encroachment of the foramen due to cervical spondylosis or other cause of degeneration, whereas HNP is much less frequent (20-25 %) and tumors and other causes even less frequent. Pain occurs only if the dorsal root ganglion (DRG) is compressed. Hypoxia of the nerve root and DRG exacerbates the pain. Inflammatory mediators including MMP's, PGE2, IL6 and NO. Nonsurgical management resolution correlates with imaging improvement.

Neck and arm pain predominate. Sensory symptoms (burning, tingling) follow a dermatomal distribution, but pain follows a myotomal pattern. C7 pain for example includes radicular pain to forearm, and N/T to the third digit. Pain is relieved by looking to opposite contralateral side and holding hand on top of the hand and exacerbated by turning the head towards the pain. Red flags including systemic signs of illness (fever, chills, weight loss), diffuse hand numbness attributed to CTS, clumsiness, urinary urgency or frequency not retention or incontinence. Provocative tests for radiculopathy are mostly unreliable. C7 is most commonly affected followed by C6.

Signs of C5 involvement include pain in the medial scapular border radiating to the elbow, weakness of the deltoid, supraspinatus and infraspinatus, sensory loss in the lateral arm, and loss of the supinator reflex.Signs of C6 involvement include pain in lateral forearm, thumb and index finger, weak biceps, b-r, and wrist extensors, thumb and index finger sensory loss and loss of biceps reflex.

Signs of C7 involvement ae pain in medial scapula, posterior arm, dorsum of forearm, third finger, weak triceps, wrist flexors, finger extesnors, sensory loss in posterior forear and third finger, and loss of triceps reflex.

Signs of C8 involvementare pain in shoulder, ular side of forearm, fifth finger, weak thumb flexors, abductors, and intrinsic hand muscles,and sensory loss of the fifth finger.

Treatment is not proved in large trials. Analgesics including opiates and NSIAA's are first line sometimes with prednisone. Epidural injections result in relief that is longstanding in many patients but complications include spinal cord and brainstem infarction. Hard/soft cervical collar for short term or cervical pillow at night are used. Cervical traction is unproved. Exercise therapy including active AROM, aerobic conditioning with isometric and progressive resistive exercises are usually recommended after initial period.

Indications for surgery include cervical root compression on imaging, concordant pain or dysfunction, persisting pain, or functional motor deficit, or compression of the cord. Anterior decompression with strut reconstruction is common.

Clinical feature and prognostic factors in adults with bacterial meningitis

van de Beek B, de Gans J, Spanjaard L et al. NEJM 2004; 351: 1849-59. Dutch study analysed 696 cases of community acquired acute bacterial meningitis seen 1998-2002. The classic triad of neck stiffness, fever, and change of mental status was seen in only 44 %, but 95 % had two of the four symptoms (the fourth symptom being headache). Mortality was 21 % and much higher with pc meningitis than mc meningitis (30 v. 7 %). Risk factors (negative risk) were advanced age, present otitis or sinusitis, absent rash, low GCS on admission, tachycardia, positive blood culture, elevated sed rate, thrombocytopenia, and low CSF WBC. Worst risk thus was with systemic compromise, low level of consciousness and infection with SC.

In more detail, HA occurred in 83 %, fever in 77 %, change in mental status in 69 % (GCS <14). Rash was present in 26 % and usually indicated mc infection (98 % of time) . 89 % of rashes were petechial. Only 3 % of those with information had papilledema.

Discussion of steroids: The european dexamethasone study showed adjunctive treatment with corticosteroids was beneficial although a posthoc analysis showed it to be more likely due to reduction in systemic than neurologic complications.

HABC Hypomyelination of basal ganglia nad cerebellum

van der Kmaap MS, Linnannkivi T, Paetau A et al. Hypomyelination with atrophy of the basal ganglia and cerebellum: followup and pathology. Neurology 2007; 69: 166-171.

A report of 11 new patients is made. Typically a pediatric population presented with normal or delayed psychomotor development, with increasing extrapyramidal movement disorders, spasticity and ataxia. The putamen was small or absent, the caudate often atrophic with normal thalamus and globus pallidus. The cerebellar granular layer was typically affected. All known patients were sporadic. This is a recently described syndrome (2002) with less than 20 reported cases.

Impulse control and PD Quick hits AAN 2008

1. Patients with PD showed altered decision making under ambiguity but had preserved decision making under risk conditions with explicit rules for gains and loss.
2. Acamprosate was used to treat impulse control disorders in 2 patients with PD in whom discontinuation of dopaminergic drugs did not help. It worked
3. Topiramate was used in 8 Spanish patients to reduce ICD and it appeared to work.
4. The ICD spectrum included pathological gambling, hypersexuality, shopping, computer use and binge craving of sweets, which should be specifically sought in the history taking.

AAN 2010
Hoarding may be a component of the syndrome

Neuroopthalmic findings that reliably differentiate PSP and PD

P05.042 AAN book 2008 Brad Katz et al. Salt Lake City Utah

In addition to standard criteria , the following differentiated the 2 disorders: slowed horizontal saccades, square wave jerks, eyelid opening apraxia, abnormal vertical OKN's, lid retraction stare, blink rate and light sensitivity were all implicated. A cutoff score of 2 or more of the the following three features: greater than 5 swj's, abnormal OKN's downward, and lid retraction stare identified all of 28 patients correctly (including placebos).

Hardwick A, Rucker JC, Cohen ML, et al.  Evolution of oculomotor and clinical findings in autopsy proven Richardson syndrome.  Neurology 73; 2122-2123 2009.

Authors note the SPEED of vertical saccades (more than amplitude) remain the cornerstone for differentiating PSP from other disorders.  Clinical presentation was young, absent falls, complaints of horizontal diplopia due to vergence abnormalities, cognition c/w FTD.  At autopsy atrophy was restricted to the superior colliculi with rare NFTs.

Hemiparkinson-hemiatrophy syndrome

Wijemann S, Jankovic J. Hemiparkinsonism-hemiatrophy syndrome. Neurology 2007; 69: 1585-1594.

Seminal description was made by Klawans in 1981 (Neurology) with hemiatrophy beginning in childhood and hemiParkinsons beginning in early adulthood (before 45). The hemiatrophy may be unnoticed. Symptoms usually begin ipsilateral to the hemiplegia but may spread to the other side. The condition may progress slowly and respond variably to levodopa. This series of 30 patients is the largest to date published. Patients may present initially with dystonia, that is often action induced and may involve the leg or arm only, induced by walking, running, or writing. There was no right or left sided predominance. Patients could present however, with early morning dystonia, tremor, bradykinesia, or gait imbalance. Patients often had scapular winging, raised shoulder , unequal leg length, brisk reflexes and extensor plantars. Occassionally patients had problems in pregnancy or early development especially walking. Scoliosis was common. MRI findings include asymmetric lateral ventricles, volume loss, thalamic or arachnoid cyst. Unilateral changes including calvarial thickening, expansion of the ethmoid, frontal or mastoid sinus, and elevation of the petrous ridge and greater wing of the sphenoid as in the Dyke Davidoff Mason syndrome are reported.

Negative signs and symptoms, that is thsoe infrequently or not seen, include axial signs such as swallowing or speech difficulty or symmetric freezing (although one patient had a relatively unusual sign of unilateral freezing).

The hemiatrophy involved, in order of frequency, hands, feet and face. Some patients first noted difficulty fitting shoes. Its developmental character differentiates it from atrophic conditions such as the Parry Romber syndrome or linear scleroderma. Perinatal injuries are not universal and some cases are traumatic, such as a patient who suffered a gunshot wound to the head at age 6.

Genetic mutations such as the parkin mutation are reported, albeit rarely.

Surgery has been used including VIM DBS, bilateral STN DBS

The authors speculate that patients might have less dopaminergic neurons at birth, perhaps due to a toxin such as lipopolysaccharide, paraquat, or fungicide maneb.