DADS

more pn miscellany

rituxan is useful? in DADS

distal acquired demyelinating sensory neuropathy (DADS),  M protein differentiates from classical CIDP as does (lack of ) response to treatment. Is large fiber neuropathy in men in fifties or above.  Half have anti MAG antibodies, poor response to IVIG.  Differentiate DADS-M (monoclonal paraproteinemia present) from DADS no M which is sensory CIDP. 

Miscellany on neuropathy & tests

from Saperstein
B12--may cccur suddenly, 11% hands, 75 % hands and feet, 42 % PN. In evaluating, recall that MMA is increased in renal disease and volume depletion, homocystein in hypothyroidism, age, genetic syndromes, pyridoxine deficiency.

MGUS incidence of monoclonal proteins in population above 50 is 1 %, above 70 is 3 %, in patients with PN is 10 %. SPEP misses 10 percent caught by SIFE. 30 % of MGUS patients eventually develop something (MM, WM, Amyloid). Quantify M protein should be less than 3 g/dl. +/- BM biopsy. Axonal EMG not as bad. DADS also called demyelinating PN, "CIDP" (wrong) IGM neuropathy and anti MAG neuropathy. Usually occurs in older males (> 60). Sensory ataxia, PROLONGED LATENCIES ON NCS are typical. Consider fat biopsy if cardiac,renal, or disease is present.

Celiac disease-- note there are cases with negative duodenal biopsies. Antigliadin antibodies are present in 5-12 percent of normals, but transglutaminase antibodies are more specific. No response to IVIG or poor response to gluten free diet but do it anyway.

antiHU antibodies are best saved for patients with cerebellar ataxia or encephalopathy. NCS show sensorimotor pattern. Less known antibody is CD@ also known as CRMP (collapsing response mediator protein 5). Consider lung cancer, thymoma.

GM1 antibody associates with multifocal motor neuropathy, or at low titers other AI neuropathies not seen in MADSAM.

antiMAG-- small pct dont have igm

Barohn's PN phenotypes

1. Symmetric proximal and distal weakness with sensory loss. GBS or CIDP, is treatable

2. Symmetric distal sensory loss with or without weakness. This is untreatable with immunomodulators and is the most common PN. Within category the most common types are CSPN (cryptogenic sensory peripheral neuropathy) and metabolic, a category that includes diabetic neuropathy and alcoholic neuropathy. Rarer causes include hereditary sensory neuropathies.

3. Asymmetric distal weakness with sensory loss. This includes mononeuritis multiplex, consider vasculitis, motor sensory variant and HNPP (hereditary nerve pressure palsies) or MADSAM (multifocal acquired distal sensory and motor neuropathy, or Lewis Sumner syndrome) which is diagnosed with EMG. Rarer causes are infection (HIV, sarcoid, lyme) or involvement of single nerves or roots (eg. CTS).

4. Asymmetric proximal and distal weakness with sensory loss. Proximal means it may include elbow extensors, hip girdle muscles, neck muscles, knees, covering c5-T1 or L2-S1). Consider polyradiculopathy or plexopathy, due to DM, plexopathies, polyradiculopathy due to neoplasia, carcinoma, lymphoma, and hereditary neuropathy

5. Asymmetric distal weakness without sensory loss eg. progressive footdrop. Category includes ALS (especially with UMN signs), progressive muscular atrophy including regional forms (brachial or leg) juvenile monomelic atrophy, multifocal acquired motor neuropathy

6. Symmetric sensory loss (like number 2) but with UMN signs (crossed adductors, Babinski) think B12 deficiency, ALD, MLD or combination of diabetic/CSPN with cervical spondylosis diagnosis of exclusion)

7. Symmetric weakness without sensory loss-- consider SMA (Kennedy s. includes bulbar, chromosome five includes neck weakness). With bilateral footdrop may have normal EMG. CMT SNAPs are abnormal. overlaps MD and NMJ

8. Focal midline proximal symmetric weakness with neck extensor weakness (ALS, myopathy, MG, oculopharyngeal d., Kennedy s.)

9. Sensory asymmetric proprioceptive loss without weakness. Looks like neuronopathy (CA) but NORMAL SNAPS, abnormal roots on MRI suggest autoimmune, +/- treat with IVIG

10. Autonomic dysfunction

Exceptions to above
1) Mononeuritis multiplex including vasculitis presents symmetrically in one third

2) CIDP -- MMN and MADSAM may be asymmetric distal

3) Demyelinating CMT has no proximal weakness

4) DADS phenotype looks like pattern 2 at bedside but on exam has prolonged latiencies.

SE III

Status epilepticus is a neurologic emergency. The first item is medical stablization airway-breathing-circulation. Confused patients should be given thiamine, then glucose (50 grams_, thiamine (100 mg i-v), Narcan (0.4-2.0 mg i-v), and flumazenil (if indicated) 0.2 mg i-v. Labs should be sent, including electrolytes, CBC, diff, Ca, Mg, PO4, extra red top, AED levels, tox screen/ ETOH level.
Several drugs may be used for the acute treatment of SE, but the key is knowing in detail the pharmacokinetic proporties of the chosen drugs. Lorazepam is often given first line, and is considered the most rapidly effective. The dose is 0.5-1.0 mg/kg, Unlike diazepam, is not metabolized by the liver and has a longer half life. Typically, if lorazepam is used a longer acting drug needs to be added immediately. Cerebyx can be given i-v. Unlike i-v Dilantin, Cerebyx can be given rapidly, without cardiac monitoring, can be given i-m if no i-v access is obtained, and does not cause purple hand syndrome (safer and more effective), Dosing is identical to Dilantin. IT IS NOT ONE GRAM. The dosing is 20 mg/kg, about 1500 grams in an average sized patient, and underdosing can cause recurrent seizures. In patients with verified diagnosis of overt GCSE, response rates were as follows: lorazepam, 64.9%; phenobarbital, 58.2%; diazepam and phenytoin, 55.8%; and phenytoin alone, 43.6%. In statistical comparison of the pairs, only the difference between lorazepam and phenytoin alone was significant.
If the patient has a single seizure and is able to swallow pills, they may be orally loaded with Dilantin Kapseals, 100 mg tablets in the 20 mg/kg dosing schedule. Typically for a 80 kg man, 400 mg po q 3 hours times four doses is reasonable. A Dilantin level should be checked the following morning and a daily dose ordered. LIQUID DILANTIN GIVEN THROUGH DOBHOFFS NEVER ACHIEVES THERAPEUTIC LEVELS! (Give Kapseals or i-v Cerebyx).
Alternatives: Depacon (= i-v Depakote) 20 mg/kg i-v over five minutes, phenobarbital 10-20 mg/kg i-v with monitoring over an hour. In refractory SE (ie, that which does not respond to either regimen above), a commonly used protocol is intravenous pentobarbital. A loading dose of 5 mg/kg is followed by 0.5-3 mg/kg/h titrated to cessation of seizures or a burst-suppression pattern on EEG. In a recent study of patients with refractory SE, Krishnamurthy and Drislane concluded that the survival rate was better in patients whose EEG was more suppressed. Hypotension is a risk of pentobarbital infusion. In patients who cannot tolerate pentobarbital, alternatives include continuous infusion of benzodiazepines (eg, midazolam or propofol).
Pitfalls
1. Failure to perform EEG-- may miss nonconvulsive SE and the chance to treat. May miss pseudoseizures and overtreat patient.
2. Failure to perform lumbar puncture-- may miss meningitis
3. Failure to consider a diagnosis of herpes encephalitis-- must be treated early
4. Using above medications incorrectly
5. Failure to order EEG monitoring on admission if patient is not back to normal-- similar to 1-- may miss ongoing SE
6. Discharge from ER prior to patient returning to baseline cognitively-- may miss HSVE
7. Failure to consider differential diagnosis-- intoxication, locked in syndrome, psychogenic SE etc.
Complex partial status epilepticus
Favorable neurologic outcomes of CPSE have been reported regardless of whether medical treatment was successful. Few reports indicate serious sequelae complicating CPSE. Thus, the question of how aggressively to treat CPSE remains controversial. In general, pending a good, randomized trial, CPSE should be treated similarly to GCSE, except that treatment should stop before the use of general anesthesia (eg, pentobarbital coma).
In acute stages and for diagnosis, treatment with an intravenous benzodiazepine may be helpful. Often, out-of-hospital treatment with rectal or oral benzodiazepines aborts an episode. Williamson believes that, since most patients with CPSE have a history of epilepsy, concomitant AED therapy should be optimized.
Walker and Shorvon reported that, although most episodes of CPSE are self-terminating, recurrent episodes are encountered, and medical treatment is often disappointing. Patients who have medically refractory localization-related epilepsy should be evaluated for surgical therapy.
Absence status epilepticus
Walker and Shorvon reported that ASE responds rapidly to intravenous benzodiazepines. D'Agostino and coworkers believe that valproate is the medication of choice for ASE. Although effective, this treatment may result in complications such as sedation and respiratory depression. Kaplan summarized a case of a female with known absence epilepsy in which hospitalization was avoided by treating ASE with intravenous valproate. Snead et al stated that the more atypical the SE, the more difficult it is to control with benzodiazepines and other forms of therapy. Patients with primary generalized epilepsy should have optimized valproate or ethosuximide therapy to prevent recurrent episodes of ASE. Thomas et al reported that long-term anticonvulsant therapy might not be necessary in adults who are middle-aged or older at the onset of de novo ASE.

Li

SE II

Status epilepticus is a neurologic emergency. The first item is medical stablization airway-breathing-circulation. Confused patients should be given thiamine, then glucose (50 grams_, thiamine (100 mg i-v), Narcan (0.4-2.0 mg i-v), and flumazenil (if indicated) 0.2 mg i-v. Labs should be sent, including electrolytes, CBC, diff, Ca, Mg, PO4, extra red top, AED levels, tox screen/ ETOH level.
Several drugs may be used for the acute treatment of SE, but the key is knowing in detail the pharmacokinetic proporties of the chosen drugs. Lorazepam is often given first line, and is considered the most rapidly effective. The dose is 0.5-1.0 mg/kg, Unlike diazepam, is not metabolized by the liver and has a longer half life. Typically, if lorazepam is used a longer acting drug needs to be added immediately. Cerebyx can be given i-v. Unlike i-v Dilantin, Cerebyx can be given rapidly, without cardiac monitoring, can be given i-m if no i-v access is obtained, and does not cause purple hand syndrome (safer and more effective), Dosing is identical to Dilantin. IT IS NOT ONE GRAM. The dosing is 20 mg/kg, about 1500 grams in an average sized patient, and underdosing can cause recurrent seizures. In patients with verified diagnosis of overt GCSE, response rates were as follows: lorazepam, 64.9%; phenobarbital, 58.2%; diazepam and phenytoin, 55.8%; and phenytoin alone, 43.6%. In statistical comparison of the pairs, only the difference between lorazepam and phenytoin alone was significant.
If the patient has a single seizure and is able to swallow pills, they may be orally loaded with Dilantin Kapseals, 100 mg tablets in the 20 mg/kg dosing schedule. Typically for a 80 kg man, 400 mg po q 3 hours times four doses is reasonable. A Dilantin level should be checked the following morning and a daily dose ordered. LIQUID DILANTIN GIVEN THROUGH DOBHOFFS NEVER ACHIEVES THERAPEUTIC LEVELS! (Give Kapseals or i-v Cerebyx).
Alternatives: Depacon (= i-v Depakote) 20 mg/kg i-v over five minutes, phenobarbital 10-20 mg/kg i-v with monitoring over an hour. In refractory SE (ie, that which does not respond to either regimen above), a commonly used protocol is intravenous pentobarbital. A loading dose of 5 mg/kg is followed by 0.5-3 mg/kg/h titrated to cessation of seizures or a burst-suppression pattern on EEG. In a recent study of patients with refractory SE, Krishnamurthy and Drislane concluded that the survival rate was better in patients whose EEG was more suppressed. Hypotension is a risk of pentobarbital infusion. In patients who cannot tolerate pentobarbital, alternatives include continuous infusion of benzodiazepines (eg, midazolam or propofol).
Pitfalls
1. Failure to perform EEG-- may miss nonconvulsive SE and the chance to treat. May miss pseudoseizures and overtreat patient.
2. Failure to perform lumbar puncture-- may miss meningitis
3. Failure to consider a diagnosis of herpes encephalitis-- must be treated early
4. Using above medications incorrectly
5. Failure to order EEG monitoring on admission if patient is not back to normal-- similar to 1-- may miss ongoing SE
6. Discharge from ER prior to patient returning to baseline cognitively-- may miss HSVE
7. Failure to consider differential diagnosis-- intoxication, locked in syndrome, psychogenic SE etc.
Complex partial status epilepticus
Favorable neurologic outcomes of CPSE have been reported regardless of whether medical treatment was successful. Few reports indicate serious sequelae complicating CPSE. Thus, the question of how aggressively to treat CPSE remains controversial. In general, pending a good, randomized trial, CPSE should be treated similarly to GCSE, except that treatment should stop before the use of general anesthesia (eg, pentobarbital coma).
In acute stages and for diagnosis, treatment with an intravenous benzodiazepine may be helpful. Often, out-of-hospital treatment with rectal or oral benzodiazepines aborts an episode. Williamson believes that, since most patients with CPSE have a history of epilepsy, concomitant AED therapy should be optimized.
Walker and Shorvon reported that, although most episodes of CPSE are self-terminating, recurrent episodes are encountered, and medical treatment is often disappointing. Patients who have medically refractory localization-related epilepsy should be evaluated for surgical therapy.
Absence status epilepticus
Walker and Shorvon reported that ASE responds rapidly to intravenous benzodiazepines. D'Agostino and coworkers believe that valproate is the medication of choice for ASE. Although effective, this treatment may result in complications such as sedation and respiratory depression. Kaplan summarized a case of a female with known absence epilepsy in which hospitalization was avoided by treating ASE with intravenous valproate. Snead et al stated that the more atypical the SE, the more difficult it is to control with benzodiazepines and other forms of therapy. Patients with primary generalized epilepsy should have optimized valproate or ethosuximide therapy to prevent recurrent episodes of ASE. Thomas et al reported that long-term anticonvulsant therapy might not be necessary in adults who are middle-aged or older at the onset of de novo ASE.