MGUS Pearls

from Ramchandren S, Lewis RA.  Monoclonal gammopathy and neuropathy.  Curr Opin Neurol 2009; 22:480-485.

Note-  search this blog for "MGUS" and various information posted elsewhere will not be repeated

Pearl -  Differentiate into subtypes based on type of proteins found, and clinical syndromes

eg.  osteosclerotic myeloma has an 85-100 % incidence of neuropathy, depending on whether they have partial syndrome or full POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M spike and skin changes).  In myeloma one third of patients have subclinical PN, and half of these may be small fiber neuropathy, in others, NCS and EMG is required to detect.  In contrast, PN is much less frequent in Waldenstrom's macroglobulinemia (5-10 %) and amyloidosis (17 %). 

IgM paraprotein patients have half of patients with paraprotein and neuropathy, and 15 % of those with paraprotein and no neuropathy. IgG patients only have 35 % of patients with paraprotein and neuropathy, but 75 % of patients with paraprotein and no neuropathy.  IgA patients have 15 % of those with paraprotein and neuropathy, 10 % of those with paraprotein and no neuropathy.   Thus IgM is NOT the most common paraprotein, but is the most common to cause neuropathy.  Most have MGUS, a few haveWaldenstrom's and  other lymphoproliferative disorders.  IgM binds myelin sheath and neural antigens in patients with IgM and neuropathy, not in those with IgM and no neuropathy.  Of those with IgM paraprotein and neuropathy, half have anti MAG antibodies.  Electron microscopy shows deposition on myelin and separation of myelin by MAG via complement.  Reducing anti MAG IgM also improves the neuropathy. 

IgG paraprotein patients are as above, less likely to develop PN by far, and those that do have all types of neuropathies (distal , length dependent axonal and CIDP).  CIDP patients with IgG paraprotein are otherwise identical to those CIDP patients without IgG paraprotein.  Unless in a patient with myeloma, amyloid or POEMS, IgG paraprotein is likely to be incidental.  A few patients with IgG or IgA paraprotein also have deposition on myelin like IgM patients so previous statement is not absolute.

IgM paraprotein patients with PN usually have kappa light chains and half have anti MAG antibodies.  They are older males (60s) with "DADS" which stands for "distal acquired demyelinating sensory neuropathy."  Large fibers affecting VS and proprioception cause problems with balance that are progressive.  DADS M (DADS with an IgM paraprotein) is probably distinct from DADS no M.  A few patients have an aggressive course.  EMG in DADS M has accentuated distal slowing and long latency motor nerves and attenuated or absent sensory nerves. 

IgG/IgA MGUS have no homogenous presentation, but usually have less balance problems. 

2. Myeloma patients have peripheral neuropathy due to perineural or perivascular IgG kappa deposition, or treatment related neuropathy.  IgM paraprotein is seen rarely in myeloma, and have sensory > motor symptoms.  If amyloid is present, its more likely to be painful.  EP is more likely to show axonal damage, but may show demyelinating sometimes.No intervention changes PN but therapy of MM exacerbates PN. 

3.  POEMS-- Paraprotein is usually IgA or IgG lambda.  Synonyms for condition are Crow-Fukase syndrome or Takatsuki syndrome.  Patients are younger (40s) with severe sensory and motor features.  Presentation is progressive distal weakness, paresthesias, and numbness more often than CIDP like.  Weakness if usually in ankles most severely.  Patients are wheelchair bound within a year.  There is 40 % mortality at five years.  EMG shows demyelination with secondary axonal loss. Conduction block is rare. Nerve biopsy can show endoneurial deposits.  Treatment is for underlying, and PN is reversible for localized process such as plasmacytoma.  High dose chemotherapy with autologous blood stem cell rescue is being explored.  Misdiagnosed early as CIDP.  Diagnosis of: demyelinating PN, monoclonal gammopathy and one of the three:  osteosclerotic myeloma, Castleman's disease or increased VEGF.  Also must have one or more of following:  organomegaly, endocrine dysfunction, edema , skin changes (hypertrichosis or hyperpigmentation), papilledema, thrombocytosis, polycythemia). 

4.  Waldenstrom's is rarely associated with PN but when it is, its usually IgM kappa with or withour anti MAG antibodies.  Its clinically indistinguishable from MGUS related PN with anti MAG or DADS M.  Responds to plasma exchange since IgM paraprotein is intravascular, may also use steroids and alkylating agents and Rituxan.

5.  Amyloidosis PN is usually present for a long time first.  A. is a multisystem disorder with IgG or IgA lambda paraproteins and deposition of light chains in target organs.  Either vascular insufficiency or toxicity of amyloid causes the PN.  Painful progressive distal sensory and motor PN  often with autonomic findings is seen.  NCS show axonal sensory > motor neuropathy.  Mean prognosis is 25 months. 

6.  Patients with DADS and IgG or IgA MGUS respond to treatment regimens used for CIDP patients without MGUS.  DADS M polyneuropathy may be misdiagnosed as CIDP but respond more poorly to treatment regimens used for CIDP.

7.  CANOMAD is a rare disorder (chronic ataxic neuropathy with opthalmoplegia, M protein, cold agglutinins, and anti disialosyl antibodies against gangliosides, including GD1b, GD3, GQ1b, and GT1b.  There is a chronic PN with sensory ataxia and areflexia, with sparing of strength.  Its similar to Miller Fisher syndrome that has antibodies to GQ1b, but is chronic and progressive rather than monophasic and acute. 

Normal pressure hydrocephalus assessments

Questionnaire/assessment: (from the Neurologist)
http://neuropsychminutiae.blogspot.com/2010/07/nph-questionnaires-for-initial.html

Guidelines for the Initial Management of NPH (published in Neurosurgery)  2005; 57:3.

Links, support groups, information, etc.
http://www.ninds.nih.gov/disorders/normal_pressure_hydrocephalus/normal_pressure_hydrocephalus.htm


Well done powerpoint presentation
http://www.usafp.org/USAFP-Lectures/2007-Lectures/16%20March%20-%20Friday/Ryan%20-%20NPHredo.ppt

MRI criteria:

1. Maximal frontal horn width divided by diameter of inner table, usually >.33, but often > .4
2. Lack cortical/hippocampal atrophy/extensive white matter lesions
3. Callosal angle > 40 degrees
4. Altered brain water content
5. Aqueductal and fourth ventricular flow void on MRI

Gait criteria:  At least two of the following

1. Gait/Balance- at least two of following present
2. Decreased step height
3. Decreased step length
4. Decreased cadence/speed
5. Decreased trunk sway
6. Widened stance
7. Toes turned outward while walking
8. En bloc turning- turns take three or more steps
9. Impaired balance- two or more corrective steps for eight steps on tandem gait testing

Cognition (at least two of following)

1. Cognition- two of following present
2. Psychomotor slowing
3. Decreased fine motor speed
4. Decreased fine motor accuracy
5. Difficulty dividing or maintaining attention
6. Impaired recall especially for recent events
7. Impairment of executive functions- multi-step procedures, working memory, formulation of abstractions, insight
8. Behavioral or personality changes

Urinary symptoms: one of following

 

1. Episodic urinary incontinence not attributable to other causes
2. Persistent urinary incontinence
3. Fecal and urinary incontinence

OR  One of following

1. Urinary urgency
2. Urinary frequency- 6 or more voids in 12 hour period
3. Nocturia- more than two voids in night

 Clinical diagnosis

Probable iNPH:  Gait or balance impairment, plus cognitive or bladder control disturbance, or both.  MRI shows an Evans ratio of greater than .3 with no evidence of obstruction.  Diagnosis based on probable NPH predictes 48-64 % of time a good response to surgery.

 

Possible iNPHL  Urinary or cognitive impairment without gait impairment

 

Pearls:

1. Rely on family assessment as much as what patient says about gait assessment
2. Levodopa trial occassionally needed to sort out festination
3. TInetti Assessment Scale (TAT) for gait assessment screening has a B level of evidence from AAN reviews  and is found here:  http://agrc.ucsf.edu/files/Tinetti%20AssessmentTool%20(gait%20and%20balance%20test)%20(Week%202%20-Mobility).pdf
4. TAT misses a velocity component for gait assessment so also use TUG (timed get up and go) and is found here http://www.dhmc.org/dhmc-internet-upload/file_collection/tug_0109.pdf that also has a Level B evidence from AAN
5. Other instruments that can be used are the ten minute walk, Berg balance test  http://www.fallpreventiontaskforce.org/pdf/BergBalanceScale.pdf  and the Short Physical Performance Battery   http://www.grc.nia.nih.gov/branches/ledb/sppb/index.htm
6. Urinary incontinence may be described as urinating just before reaching the toilet
7. Cognitive differentiation from Alzheimer's disease can be accomplished by testing that includes factors that innclude components that should not be affected by NPH, such as Boston Naming Test (in addition to findings that would be affected such as letter fluency and memory and executive function)
8. Atypical presentations in young may include headache, and poor job performance rather than memory loss.
9. Obstruction of aqueduct or fourth ventricle due to "late onset aqueductal stenosis" may improve with endoscopic third ventriculostomy (ETV).  These patients should NOT undergo LP due to risk of herniation
10. Thinned /  distended callosum may predict shunt responsiveness, may be seen as "bowing" on sagittal views
11. Presence of "B" waves and increased pulse amplitudes correlate with symptomatic iNPH and responsiveness to shunting.  Authors use 48 hours of monitoring followed by 72 hours of drainage.
12. Behaviorally and by fMRI, increased Stroop testing and finger tapping correlates with SMA functional activity
13. Response to serial LP's correlates with 88 % response to surgery.  Can measure with Tinetti and TUG tests (links above) .  With high volume tap, expect improvement in velocity, turning, stride length, number of steps to turn, and tendency to fall, among others.  Test immediately before and after shunt, and again q 2-4 hours.  Consecutive day LP's x 3 days increased sensitivity to 88 %. 
14. ELD (extended lumbar drainage x 3 days) if no response, very few patients will benefit from surgery.
15. With ELF and physiologic measurements, authors claim 75-90 % improvement in first year after shunting, and 80 % sustained improvement after two years, with substantial overall Medicare expenditure savings. 
16. If a programmable shunt is used, the billing code is 62252
17. Obviously need a good neurologist to make the diagnosis and exclude various neurodegenerative diseases

Coin rotation test validation

 

Hill BD et al. The Neurologist. 2010; 16: 249-253

 

Authors validate a longstanding easy test for fine motor processing used for decades at LSU in 86 normals.  Task consists of counting number of 180 degree rotations of a quarter in ten seconds by the dominant and nondominant hands.  A correction for drops is used, but not that important.  Task is to rotate a quarter using thumb and fingers one and two in ten seconds with an examiner using a timer and counting.  If the coin is dropped, the subject gets another ten seconds.  The adjusted score is the number of rotations in ten seconds minus (0.1 x rotations x drops).  Traditionally, LSU has used a cut score of ten to indicate impairment.  Authors believe a cut score (for both hands) of 13 is better, with increased sensitivity and some loss of specificity.

 

Risk of falling in Parkinson's disease patients

from Kerr et al. Neurology 2010; 75: 116=124

Authors looked at 101 independently living patients without walking aids and put various factors through a computer to predict risk of falling.  The factors that increased the risk include

• dyskinesias
• symptomatic orthostasis
• sleep disturbance
• Tinetti, Berg, and TUG (timed up and go) measurements
• poor peripheral sensation and knee extension strength and greater a-p sway when standing on firm surface
• UPDRS total score and FOG (freezing) questionnaire
• For previous nonfallers, key measurement was A-P sway on firm surface as risk for future conversion to falling
• UPDRS factors that were most important were rising from chair, rapid alternating movements and leg agility

Billing pearls (Random)

1.  Never write "benign" positional vertigo, its "paroxysmal" positional vertigo unless you want to be downcoded.

2.  Discharge day codes 99238 for less than 30 minutes, 99239 for more than 30 minutes, document time including spent at nursing station doing prescriptions, need not be continuous.

3.  Critical care codes  99291, 99292 for first hour (minutes 31-74) and each additional 30 minutes, respectively.  Must MANAGE some critical aspect of care and not just consult.  Use different ICD9 code than the attending if you are not primary on case.  Time need not be continuous, and time spent off unit eg. looking at X rays with radiologist counts, unlike floor patients.  Aggregate time with partners if applicable.  This is appropriate for er tpa administration.

4.  Prolonged care codes 99356, 99357 for INPATIENTS for first hour (minutes 31-74 and each additional half hour respectively.  Document reason for prolonged service, submit note to carrier, list start and end clock time required.  Time spent off unit eg radiology does not count, but time spent on unit coordinating care counts.

5.  Prolonged care codes 99354, 99355 are analagous to (4) above except they are for outpatients and Face to face time (start and end clock time) must be documented along with reason. 

6.  Modifier 25 for procedure same day as an E/M service usually EEG and EMG are exempt.

7.  Documentation for high level visit: Indicate chronic illness with severe exacerbation and/or side effects such as MS exacerbation, seizure, Dilantin toxicity (if you are still using Dilantin), risk of Morbidity and mortality (INR high in stroke patient), Abrupt neuro change (TIA, seizure, AMS). 

Must include in note  1) 1 new problem needing additional assessment  or 2) 2 old problems inadequately controlled .  Document at least a three way differential (Alzheimer's v. frontotemporal v. LBD?; or MS v. CIS v. ON due to sarcoid).  Document at least 3 management options (Copaxone, Rebif, Betaseron; steroids; gabapentin: Detrol   or    Aggrenox v. Plavix v Asa, lipitor v. simvastatin; SQ heparin to prevent DVT's).   or iv (parenteral) controlled substances.

New consults need CC, 4 facts for HPI, 1 fact each for PSF (past, family, social history), 10 point ROS (see below), 23 point Neuro SSE (see below). 

8.  Office followup high level requires  CC, 4 facts HPI, med list, social fact, 10 point ROS (may sign and date patient form containing some of these), PLANS (labs, meds, to address problem).   midlevel office visit requires CC, 4 point HPI, mention some PMH or current meds, 2 system ROS, palns to address problem (1-2 chronic problems of moderate degree, or uncertainty re risk or prognosis).  Level 3, low level requires a self limited stable problem eg chronic pain needing E/M, CC, pertinent positives and negatives, and PLANS to address problem.  Most documentation falls out on 3 way differential and plans. 

9.  ROS items to be covered in your office intake sheet come from the list:  constitutional, eyes, ENZT, CV, Respiratory, GI, GU, musculoskeletal, skin and or breast, neurologic, endocrine, hematologic/lymphartic, allergic/immunologic, psychiatric.  May be on a separate sheet patient fills out and checks off if MD signs and dates AND refers to it in office note.  Comprehensive ROS has 10 (TEN) items out of 14.

10.  Neuro single system exam requires 25 bulleted items, need to include 23.  These include one of three CV elements (more may be needed for care but not for documentation). The other 22 that must be included are regular parts of neuro exam.  Mandatory-- any 3 vitals (BP, HR, RR, temp, height, weight, orthostatics), general appearance, Fundoscopic exam, one of 3 cardiovascular elements (carotids, heart auscultation, peripheral vascular system), Memory (orientation, attention, recent and remote memory, language, and fund of information), CN's 2;  3,4,6; 5, 7, 8, 9, 11, 12).  CN's one and ten are not required.  Motor exam includes strength (4 ext), tone (4 ext with note of atrophy or abnormal movements), DTR's 4 ext's including pathologic reflexes, Coordination, Gait and station.  Sensory exam-- need one element of sensation recorded. 

Notes-- must document WHY you can't walk a comatose patient eg. .  Constitutional signs and vital signs can be recorded by staff.  Office needs to have an approved abbreviation list.  Note must be legible.  Templates OK, macros OK, pocket cards with elements available from AAN.

Example of a comprehensive Neuro SSE: Well developed.  120/80, HR 72, RR 16.  fundi OK no bruit.  MS: awake, alert, oriented x 3, dig 6 F, 3/3  objects at 5 minutes, nl naming and vocabulary.  CN. VFF, EOMI, facial sensation and power normal, hears well, palate.tongue midline, SCM normal.  Sens: normal PP.  Motor-- nl tone/bulk/power 4 ext. FNF, gait nl, DTR's 2+ and symmetric throughout, normal.

11,  Couselling and coordination of care may be used instead of documentation.  Counselling involves face to face discussion with patient and/or family re tests, treatments, alternatives, prognosis, education.  Coordination of care may involve interactions with other MD's or providers.  Time is key.  Documentation should state number of minutes spent face to face, that more than half time was spent on counselling and coordination of care, with some general idea of what was done.  No history or exam is needed for documentation.

12.  Be sure to document physician referring name for consults.  Be sure to document MDM in detail.