Tuesday, November 04, 2014

Definite central fourth nerve palsy

per Neil Miller

An ipsilateral or contralateral relative afferent pupillary defect (RAPD) unassociated with any decrease in visual acuity, reduced color vision, or visual defect, but with setting of an isolated fourth nerve palsy, RAPD indicated localization to brachium of superior colliculus and almost always indicates the fourth nerve paresis is central in origin.

Friday, October 17, 2014

Smartvest SQL

Chest wall oscillation approved for neuromuscular disease, 80 % paid by Medicare with assistance for rest.

originally for bronchiectasis

use for thirty minutes twice daily




topiramate tablets
divalproex delayed release tbalets
valproic acid capsules, USP
lamotrigine tablets
carbamazepine tablets
phenytoin extended release. 

receive a consistent product
use a specialty pharmacy form
MOBE referral kit available free with Rx.

Use Thrifty White Pharmacy # 61
eRx  NCPDP:3504138
fax 855 826 2596
phone 844 432 7891

Charging for items outside the traditional billing codes.

based on summary article by Orly Avitzur, Neurology Today based ona presentation by health care lawyer Daniel Brown.

New CPT codes for telephone/internet assessment when provided doctor to doctor by a consultant-- codes 99446-99449.  May be used for complex and urgent situations when face to face is not practical.  These are time based only codes and only available to consulting specialist.  MEDICARE DOES NOT PAY FOR THESE CODES, "check with commercial payors about their policies"

EMAIL (CPT code 98969 and 99444) and phone calls from patients (98966-98968 or 99441-99443) for after hours requests for routine refills of Rx and other requests.  Medicare does not cover these, because they are considered to be included in face to face.  With proper documentation, though you can add time of phone call to the time of the next visit IF its associated with the patient's next visit.  You can factor phone call into the time/complexity calculation of next visit.  Remember that using time , fifty percent of time must be face to face.   If a patient calls several moths after an appointment for an unrelated question, that could be considered a separate service.

Can doctor bill the patient directly for internet consults?  Answer is yes, but CMS "strongly encourages " and advanced beneficiary notice (ABN) before billing so patients can make an informed decision.  Also, MD must not duplicate a service performed at a subsequent visit, the components follow the descriptions in CPT code, and the services are adequately documented.

Bill for forms?  OK to bill for copying, filling forms for camp, or work UNLESS its part of that outpatient visit. 


Concise of brain antigens commonly tested

1.  NMDAR NR1  anti NMDAR encephalitis

2.  amphiphysin-- stiff person syndrome, encephalomyelitis,limbic encephalomyelitis, sensorimotor neuropathy

3.  ARHGAP 25, GRAF -- subacute inflammatory cerebellar ataxia

4. CASPR2 (contactin associated protein 2)-  Morvan syndrome, neuromyotonia, limbic encephalitis


6.  GAD 65-- stiff person syndrome, cerebellar syndrome, limbic encephalitis, epilepsy

7.  Ma2--  brainstem encephalitis, limbic encephalitis, cerebellar syndrome, polyneuropathy

8.  Yo-  brainstem encephalitis, cerebellar syndrome

9.  Ma1 -  brainstem encephalitis, limbic encephalitis, cerebellar syndrome, polyneuropathy

German study published in Ann Neurol July 23 show equal prevalence of these antibodies in healthy and diseased individuals.  Titers and Ig class distribution also were similar for above antigens.

NMDAR were found in 10-20 percent of normal individuals, and are higher among those who suffered influenza. 

Weinshenker-- Validity depends on pretest probability that patients have the illness.

Thursday, October 09, 2014

Hydroxyurea and HbF in sickle cell disease

Steinberg MH et al. Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia.    Risks and benefits up to 9 years of treatment. JAMA 1003; 289: 1645-51.  Weiner DL, et al. editorial: hydroxyurea and sickle cell disease. A chance for every patient.

HbF is inversely related to mortality in SCD, and can be increased with hydroxyurea.  Also cite Multicenter Study of hydroxyurea (MSH) in SCA (NEJM 1995; 332: 1317-1322).

299 SCA patients were randomized to hydroxyurea or placebo, morbidity was reduced by half, with no difference in mortality or stroke.  There was an open label extension of the trial on 233 patients (both arms) receiving hydroxyurea for 9 years (up to).  In this part of the study, mortality was reduced forty percent for patients receiving hydroxyurea (patient option to take or not).  Cumulative mortality corresponded with HBF levels esp .5 g/dL or higher. 

Machado Joseph disease

aka MJD, spinocerebellar ataxia type 3


adult onset, autosomal dominant
UMN and LMN signs resembling ALS may include tongue fasciculations, dystonia, rigidity, progressive external opthalmoplegia, and peripheral neuropathy.

Due to CAG triplicate repeat on chromosome 14q32.1

Cramping is far more common than in PN or SMA but not ALS and is relieved almost completely by mexilitene, supporting notion that is due to sodium conductance.

Cocaine related hallunications

Classically is the sensation of animal, bugs or insects moving under the skin (cocaine bugs or parasitosis). Other purely visual hallucinations that can occur include "snow lights" or the sensation of sunlight reflecting off snow crystals. Vibrating and pulsating geometric shapes, polyopia, and dysmorphia occur and resemble visual aura. Olfactory, tactile and gustatory hallucinations may occur. Photophobia, halos around lights, and gtrouble focusing may be due instead to pupillary mydriasis due to increased sympathetic tone.

Vienna conference return to play recommendations

Vienna conference return to play recommendations1.   Remove from game if any signs of concussion- any items missed on sideline exam
2.   No return to play in current game
3.   Medical evaluation after injury   a. rule out serious focal injury     b. neuropsychologic evaluation
4.   Stepwise return to play    a.  rest till asymptomatic      b.   light aerobic      c.  sport specific training     d.  noncontact practice      e. full contact practice     f. return to play

Shingles pearls

1. 1 in 3 people will develop HZ during their lifetimes.

2. The preeruption pain may be confused with MI , pleurisy, appendicitis, dental pain and many others.

3. Shell vial viral culture is most common test, but PCR is rapid, more sensitive and specific


Parkinsonism in cirrhotics

Burkhard PR et al. Arch Neurol 2003;60:521-528


Authors studied cirrhotics prospectively and found a unique Parkinsonian syndrome in 20 %.  Among 51 consecutive patients evaluated for liver transplant, 11 had Parkinsonism esp. stereotypical onset with generalized bradykinesia, dysarthira, postural instability, and prominent ACTION tremor.  Six had dystonia especially of face or feet.  Frontal findings were seen on neuropsych testing.  Levodopa resulted in improvement on UPDRS in 2 patietns.  CSF manganese was elevated in 3 patients in whom it was measured.  Allpatients had symmetric T1 abnormalities on MRI.  Liver transplantation reverses MRI findings.  Question arises of whether to chelate.

Wednesday, June 04, 2014

ADEM pearls

old paper, useful insights
Menge T, Hemmer B, Nessler S et al  Acute disseminated encephalomyelitis: an update. Arch Neurol 2005; 62: 1673-1680
1.  Consider a temporal relationship to a vaccine or infection.  If vaccine, especially MMR, also polioand European tick borne encephalitis vaccination

Monday, June 02, 2014

antiMOG seronegative NMO

Kitley J, Waters P, Woodhall M, et al. Neuromyelitis optica spectrum disorders with aquaphorin-4 and Myelin-oligodendrocyte glycoprotein antibodies: a comparative study.
see Levy M. Does aquaphorin-4-seronegative neuromyelitis optica exist? (editorial) JAMA Neurology 2014; 71:271-2.
Authors of both studies ferret out a subtype of seronegative NMO that is actually yet another disease.   Anti MOG positve patients with clinical features of NMO have a slightly different phenotype with features of ADEM also.  This group encompasses young males with severe episodes with better recoveries that are more likely to be monophasic, sometimes with simultaneous or rapidly sequential optic neuritis and transverse myelitis.. AntiMOG patients also had more conus involvement on spine MRI and more involvement of deep gray nuclei on brain MRI.  There were no patients with both anti MOG and anti AQU4 antibodies.  anti MOG antibodies are available at Neuroimmunology Testing Service, Oxford, England for 30 pounds).  "n" of the study was 10 aq-4 patients and 9 MOG AB patients. 
More clinical information:  4/9 anti MOG and 6/20 AQU$ AB patients had ON as initial invoolvement or part of ; anti MOG had more bilateral ON involvement (75 v. 33 %); both had severe ON when it did happen.  12/20 AQU$ 4 and 9/9 antiMOG had spinal cord involvement initially; Transverse myelitis differed with more bladder involvement in anti MOG patients as iniital symptom (33 v. 0 %) and more late sphincter disturbance in NMO ab patients.  Brain MRI was more likley to be ADEM like in MOG ab patients (44 %) v. 0 % in NMO. 

Wednesday, May 28, 2014

CJD and non CJD with neuronal markers

Grau-Rivera O, Sanchez-Valle R, Saiz A et al. Determination of neuronal antibodies in suspected and definite Creutzfeld-Jakob disease . JAMA Neurol 2014;71:74-78.

Take home points

1. A small but definite number of 346 patients with suspected CJD had anti neuronal antibody mimics but these six did not fulfil criteria for CJD. Found were NMDAR,LGI1 , CASPR2, aquaphorin 4, Tr(DNER alpha notch 4 epgf and unknown protein.

2. No patients among 46 with definite CJD had these neuronal markers.

These all were studied in CSF

Faciobrachial systolic seizures , correlate with anti VGKC and not CJD

Faciobrachial systolic seizures , correlate with anti VGKC and not CJDYoo J and Hirsch LJ. Limbic encephalitis associated with anti voltage gated potassium channel complex antibodies mimicking CJD. Jama Neurol 2014;71:79-82.

Case with following take home points:
FBDS are highly associated with ant VGKCC and not CJD and are treated with normal AED's

The two disorders otherwise may mimic each other

Anti VGKCC responds robustly to steroids

Both disorders can have elevated 14,3,3 in CSF

Absent restricted diffusion is a "red flag" against CJD

MRI of anti VGKCC is usually high T2 signal in uni or bilateral temporal lobes but they can also show cortical ribbon and basal ganglia changes mimicking CJD

FBDS mimic myoclonus but EEG confirms seizures

Spect scans show abnormal basal ganglia metabolism

Saturday, May 17, 2014

RA meningitis as stroke mimic

Bourgeois P et al.  Rheumatoid arthritis presenting with stroke like episodes. Neurology 2014; 82: 1564-5. 
70 yo male presented with series of TIA like events over ten days consisting of right leg more than arm weakness.  He had poorly controlled RA.  MRI was negative for brain parenchyma but there was enhancement of meninges and pachymeningitis.  Meningeal biopsy was positive and patient was successfully treated by Solumedrol 1 gram per day followed by 1 mg/kg/day prednisone, tapered over months with no recurrence. 
Other reported presentations of RA meningitis include cranial neuropathy and seizures.  CSF is abnormal.  Authors propose that RF in CSF is a useful biomarker if positive as false negatives occur.  Path can show 3 patterns: rheumatoid nodules, meningeal inflammation or vasculitis.
In other series there was high mortality although this patient survived.

Friday, May 16, 2014

Management of hepatic encephalopathy in hospital

Review Article
Leise MD, Poterucha J, Kamath PS et. al.  Management of hepatic encephalopathy in the hospital.  Mayo Clin Proc 2014; 89(2) 241-253.

Working Party for hepatic encephalopathy nomenclature:

Type A HE-- secondary to liver failure
Type B HE enteric hyperammonemia without liver disease
Type C  -- is associated with some liver disease.

Severity Grades
I-IV scale
0 normal
MHE normal exam,  nild changes visuoperceptive or psychometric tests
I Personality change, attention ddeficit, irritability, depressed state, tremor, dyscoordination
2  Changes sleep/wake cycle,letharygy , mood, behavioral/ cognitive changes; asterixus, ataxic gait, slow/slurred speech
3  Somnolence, confusion , disorientation, amnesia; muscle rigidity, nystagmus, clonus, Babinski sign, hyporeflexia
4  stupor and coma; oculocephalic reflexes, unresponsive

other scale SONIC (spectrum of neurocognitive impairment in cirrhoses)
covert HE (CHE) includes minimal HE (MHE) and grade I HE
overt HE encompasses grade II-IV. 

episodic HE
persistent HE impairs day to day executive function


50 percent of cirrhosis patients develop HE, and prognosis for these patients is worse even taking into account Model End Stage Liver Disease (MELD) scores.

Occurrence of OHE is approximately 22,000 per year
80 % are precipitated by an event such as GI bleed or iinfection

Most patients do not get needed maintenance care after hospital discharge

Reason for readmission is lack of education or inappropriate use of lactulose. 

Treatments- Induction therapies for episodic OHE

Nonabsorbale disaccharids-- lactulose (B galactosidofructose) and lactitol (B galactosidosorbitol) reduce ammonia by acifying colon with shift of ammonia to ammonium, shifting colonic flora from urease to nonurease producing bacterial species, and by cathartic effect.  Clinical studies are mixed/poor but its still first line in all but most sever cases.

Neomycin, metronidazole,and other antibiotics. -- neomycin is FDA approved for acute but not chronic HE to decrease gut derived bacterial derived ammonia. The evidence is weak, for OHE, and its use complicated by ototoxicity and nephrotoxicity.Possible slight benefit with metronidazole or vancomycin but each are very toxic.

Rifaximin :-- not FDA approved for episodic HE, only for secondary prevention of OHE Trials did not show substantial difference from lactitol but seemed to work faster.  RCT of rifaximin v. placebo showed benefit on composite outcome at doses of 1200-2400 mg per day for grades !-3.  May be better tolerated than lactitol.    A study of grades 3-4 with lactulose + placebo v. lactulose+ rifaximin  had more complete reversal in dual treated group (76 v. 51 %), shorter hospital stays and less ten day mortality (49 v. 24 %).

Zinc :Zinc deficiency occurs in 96 % of patients with MELD score of 12.  inc is necessary for two smmonia reduction pathways: ornithyl transcarbamylase in liver (ammonia converted to urea) and glutamine sythetase in skeletal muscle (glutamate to glutamine). One of 4 RCT's showed benefit.  Caution: zinc should be taken 2 hours before ciprofloxacin, and long term use causes copper deficiency,

L  ornithine-L aspartate : aka LOLA stimulates ammonia reduction pathways, like zinc.  Best use is in chronic HE. Has been shown to be effective, but is not available in USA

Branched chain amino acids : in cirrhosis, patients have decreased BCAA's and increased aromatic amino acids.  BCAA's are a source of glutamate which helps metabolize ammonia in skeletal muscles.  Benefits of BCAA's include better albumin synthesis, decreased insulin resistance, less hepatocellular carcinoma, and better immune function.  Studies poor quality with mixed results.  European Society for Cliical Nutrition and Metabolism recommends 1.2 g/kg / day of protein for compensated cirrhosis, and 1.5 g/kg/day for decompensated cirrhosis.  They also have grade A recommendation for standard protein supplementation for HE grade 2 or less, and BCAA for HE grades 3 and 4.

Percutaneous embolization of large portosystemic shunts :In European study , n= 37, for medically refractory patients given this, 59 % were free of HE in 100 days, 48 % in 2 years.  90 % of patients with cirrhosis improved.

Molecular adsorbent recirculating system : aka MARS based on albumin dialysis principle.  It removes protein and albumin bound toxins such as bilirubin, bile acids, nitrous oxide and enodogenous benzodiazepines, and non protein bound ammonia.  Effect on survival is in question, but HE is improved.  It is safe and tolerated and FDA approved for HE related to decompensated liver disease.  May reduce availability of certain antibbiotics and has medical contraindications.

Secondary prophylactic maintenance strategies in HE

Lactulose  : there is solid evidence for lactulose alone, or in combination with rifaximin.  Lactulose or lactulose plus probiotics had less recurrent OHE (37 5, 45 %, and 64 % respectively). 

Rifaximin :  in rifaximin v. placebo, treated group had less recurrence and rehospitalization than placebo.  It is FDA approved for secondary prevention of HE

General approach to induction and maintenance of  first episode of HE  :

1.  Screen for precipitants of OHE including GI bleed, infection, new medications such as opiods and benzodiazepines, constipation, diarrhea, dehydration, alkalosis, hypokalemia, or hypoxemia (seen in 80 % at least one).  Then manage precipitant and use lactulose also.

2.  For nonresponders, look for other precipitants, reeval the diagnosis, make sure the patient is having 3-4 stools per day.  Could then add neomycin (FDA approved but many side effects, or rifaximin which is off label. 

3. For patients who benefit use lactulose maintenance therapy especially for Child-Turcotte-Pugh class B/C

General approach to induction and maintenance of  recurrence of HE  :

1.  Same as (1) above; check number of stools with and compliance with lactulose.  Review meds

2.  If bloating or excessive diarrhea occur with any dose of lactulose, use rifaximin instead. In breakthrough HE on lactulose, add rifaximin (preferred) or neomycin (less preferred). 

3.   If breaks through on 2 drugs above, perform contrast enhanced CT to look for large intra-abdominal portosystemic shunt, or use MRA if patient is contrast risk.  Consider a shunt embolization in CTP class A cirrhosis or low MELD score (< 12-15).  60-90 percent may remit. 

4.  If embolization is not indicated consider additional treatments such as zinc, LOLA (if available), BCAA

Treatment of Severe HE grades 3-4 :

1. ABC, look for precipitants, lactulose 15-30 cc png q 1-2 hours until 3 stools achieved.  Alternative is 300 cc lactulose in 700 cc sterile water in an enema.  , may repeat prn.  Add rifaximin .  If unresponsive, perform head CT/ EEG to check diagnosis.  If diagnosis is correct, look for shunt to embolize.; if none use BCAA, zinc and LOA

MHE: Counsel patient about risks of driving

Wednesday, May 14, 2014

Fwd: MRI findings in idiopathic intracranial hypertension

From: Djacobs272@aol.com
To: dhj1.neurology@minutiae.com
Sent: 5/13/2014 2:29:27 P.M. Eastern Daylight Time
Subj: MRI findings in idiopathic intracranial hypertension

1.  empty sella
2.  flattening of posterior globes
3.  distension of perioptic subarachnoid spaces
4. narrowing of transverse venous sinuses
more from Images in Neurology JAMA Neurology 2013; 70:7937-8.

5.  distended perioptic nerve sheath
6. protrusion of the papilla 
7. "strangled optic nerve appearance
8. optic disc edema and retinal layer edema

Fwd: presentations of chronic traumatic encephalopathy


From: Djacobs272@aol.com
To: dhj1.neurology@minutiae.com
Sent: 5/13/2014 2:29:28 P.M. Eastern Daylight Time
Subj: presentations of chronic traumatic encephalopathy
Stern et al.  Neurology; 2013: 81:1122-1129
Clinical review of 36 patients, all male athletes.  They were based on autopsy studies at Boston University Center for CTAE.
11 patients had episodic memory impairment  and executive dysfunction (cognition group) initially, only later behavioral and mood disturbances.  Nine patients initially had depression and thirteen had initial behavior (explosivity, impulsivity, violence).  The behavior-mood group totalled 22.  Three patients were asymptomatic.
Age of onset of behavior / mood group was mean 51,  of cognition group, mean was 69.
Among football players, the most susceptible positions were runningback (21 %), linemen (48 %) and linebacker (10 %). 
Ten subjects were diagnosed as dementia: 10 with AD, 4 with "dementia pugilistica" or "football related" and 2 unspecified.  All 10 had stage 4 CTAE.  Seven were from the cognitive group, 2 from mood group, and 1 from behavior group. From diagnosis to death was mean 8 years. 
Mean age of onset was 57.7 years, mean age of dememntia diagnosis was 72.6 years .  4 had a history of falls, 1 of tremor.  All 10 had memory/executive dysfunction, 7 had language deficits, 2 had visuospatial deficits, 6 were described as having a "short fuse."  Mood group had 2 with predominant sadness and 2 with anxiety, 
ApoE$  homozygotes occurred more frequently than in population. 

Fwd: Secondary causes of pseudotumor cerebri syndrome

From: Djacobs272@aol.com
To: dhj1.neurology@blogger.com
Sent: 5/13/2014 2:29:28 P.M. Eastern Daylight Time
Subj: Secondary causes of pseudotumore cerebri syndrome

(from Neurology, 2013; 81:1159-1165
cerebrovenous abnormalities:
cerebral venous thrombosis (CVT)
bilateral jugular thrombosis or surgical ligation
middle ear or mastoid infection
increased right heart pressure
superior vena cava syndrome
AV fistulas
hypercoagulable states
Medications and exposures:
Antibiotics: tetracycline, minocycline, doxycycline, nalidixic acid, sulfa drugs
Vitamin A and retinoids
hypervitaminosis A, isotretinoin, all trans retinoic acid for PML, excessive liver ingestion
Hormones:  HGH, thyroxine (in children), leuprorelin acetate, levonorgestrel (Norplant), anabolic steroids
Withdrawal from chronic corticosteroids
Medical conditions
Endocrine:  Addisons, hypoparathyroidism
hypercapnia-- sleep apnea, Pickwickian syndrome
Renal failure
Turner syndrome
Down syndrome

Fwd: Diagnostic criteria for pseudotumore cerebri


From: Djacobs272@aol.com
To: dhj1.neurology@blogger.com
Sent: 5/13/2014 2:29:29 P.M. Eastern Daylight Time
Subj: Diagnostic criteria for pseudotumore cerebri
Neurology 2013; 81:1161
A.  Required
       1.  Papilledema
       2.  normal neuro exam except cranial neuropathy eg abducens palsy
       3.  Neuroimaging-- normal MRI with and without contrast
       4.  Normal CSF composition
       5.  Elevated CSF opening pressure:  , > 250 in adults > 280 in clhildren
Diagnosis of pseudotumor cerebri syndrome without papilledema
       1.  If 2-5 above are satisfied and in addition unilateral or bilateral  VI n palsy
        2.  Absent papilledema/ VI n palsy, diagnosis is suggested but not made with 3/4 imaging criteria met:  empty sella, flattened posterior globe, distended perioptic subarachnoid space with or without tortuous optic nerve, and transverse sinus stenosis.
Under research:  findings of narrowed Meckel's cave and cavernous sinuses on MRI and widened foramen ovale on CT
Uncommon manifestations:  facial paresis, hemifacial spasm, radicular pain, rhinorrhea, otorrhea, III n , IV n and general oculoparesis.
Less specific symptoms of:  headache, transient visual obscurations, pulse synchronous tinnitus, binocular diplopia, neck shoulder and back pain

Friday, April 04, 2014

Uveomeningeal syndromes: ABRA (Amyloid beta related angiitis )

Neurology 2013; 81: 1796-7

ABRA is a subtype of PCNSV (primary CNS vasculitis) with a beta pathology, found in about 18 % of biopsies showing vasculitis.  PNSV has an incidence of about 2.4 per million. Presentation is cognitive impairment, +/- seizures, focal deficits, hallucinations, multifocal or confluent T2 white matter confluence and cortical microbleeds. Often CSF protein is elevated and there is a leukocytosis.  This reported case had uveomeningeal findings clinically and on MRI. 


Neurology 2013; 81: 1596-1603

ABRA characteristics of patients:  Authors from Mayo compared  78 patients, 40 with CAA (no inflammation) and 28 with granulomatous vasculitis (ABRA) , 10 with CAA related inflammation, and 118 matched patients with PCNSV with AB seen over 25 years. 

ABRA patients were older, had more altered cognition, seizures and spells, gado positive leptomeninges, ICH, and higher CSF protein.  Response to treatment was similar.

CTM v MRI for orthostatic headache with CSF leak

Neurology 2013; 81: 1789-92. 

Authors did MRI's on 12 patients with CTM proven leaks ("gold standard" test).  11/12 had positive MRI of spine with extradural fluid collections (highly sensitive) and 6/12 having spinal dural enhancement (less sensitive).  The dura is seen as a pencil line on sagittal T1 because its displaced by fluid in the dorsal epidural space.  Other signs to be expected are brain sag, pachymeningeal enhancement, posterior fossa crowding and cerebellar tonsillar descent.

Hemosiderin deposition in brain as footprint of high altitude cerebral edema (HACE)

Neurology 2013; 81: 1776-9.

Idea- hemosiderin does not go away so patients who experience HACE have hemosiderin seen in corpus callosum-- specifically splenium-- months or years after initial injury.  37 mountaineers were studied, 8 of whom had had HACE, 11 acute mountain sickness, and 8 high clims without injury.  Unequivocal microhemorrhages were seen in 8 subjects and equivocal ones in 2 others, 1-35 months after climb.  Severe cases had microhemorrhages outside the splenium. 

Recall that HACE is vasogenic edema that is often fatal within 24-48 hours due to brain herniation.  Authors concluded that the sign of the microhemorrhages in the spleium is very specific  and the severity of the disease correlates with the severity of the microhemorrhages. 

Authors further hypothesize that microhemorrhages are a specific finding due to hypoxic insult of the blood brain barrier due to a hydrostatic leak with extravasation of red blood cells, much as occurs in lungs in patients with high altitude pulmonary edema *HAPE). 

Monday, January 20, 2014

Metformin induced B12 deficiency

Arch Int Med 2006 166: 1975-9

Retrospective study found B12 deficiency correlated with dose and duration of metformin therapy.  B12 deficit defined as less than 150.  N was 155 patients.  Mechanism is inhibition of calcium dependent ileal absorption of B12-intrinsic factor,  which calcium supplementation can reverse. 

Along with acid inhibitors (PPI's H2 blockers, metformin is most common cause of B12 deficiency.  Odds ratio is 2.88 for each i gram increment and 2.39 for use > 3 years. 

In one study 6 percent of cases of B12 deficiency had associated metformin use (Br M J 1971) ,