Biotinidase deficiency mimicking NMO: initiallyexhibiting symptoms in adulthood

Bottin L, Prud'honS, Giannesini C et al.  Multiple Sclerosis 21 (12) 1604-07 2015.  

Authors present first case of biotinidase deficiency presenting in young adulthood ; children and adolescents may present with vision loss and tetraparesis.  It was due in this case to a novel missense mutation and partly improved with oral biotin therapy.

Seropositive voltage gated calcium channels, utility

Jammoul A, Shayya L, Mente K et al.  Neurology Clinical Practice  2016; 6:409-418.

Authors differentiate "classic" group with limbic encephalitis or neuromyotonia (9.6% of total) and note the others had a panoply of diagnoses that were nonclassic.  The classic group was more likely to have high titers of ab, but there was overlap.  91 % of lcassic and 21 % of nonclassic had levels > 0.25 nM.  75 % of patietns in high level ab group had autoimmune disorders, and 75 % of patients with low level titers did not.  26 % of patients had a remote malignancy (active, remote, solid or hematologic) but not ab titer difference was noted among the groups .

Conclusions:  1.  High VGKC ab levels are found in patients with classic and other autoimmune disorderes,  Low level ab titers are seen in nonspecific and mostly nonautoimmune disorders

2.  The presence of VGKC antibodies rather than the level may serve as a marker of malignancy

Notes this is bad on a chart review of 6,032 patients who underwent evaluation .

The nonclassic group includes PNS and CNS diorders including neuropathy, dementia, ALS, CJD.  Some patietns had nonspecific symptoms such as stutering speech, nausea and vomting and orthostasis without diagnosis of neurologic disease.

Cancers were oftendiagnosed due towhole body CT/PET; 2 patietns had previously unknown cancer (Ovarian and lung).  Cancer occurred more commonly in those over age 45.  Many cases of ab finding were remote by over ten years from actual tumor.

Pearls about GQ1b

Serum and CSF GQ1 ab'sin isolated opthalmoplegic syndromes.  Spatola M, Du Pasquier R, Schluep M, et al.  Neurology 2016; 86:1780-1784

 

pearls about GQ1b from this article

 

1.  Antibodies are specific for Miller Fisher syndrome (MFS); unl;ike NMO-NMOSD, the use of the antibodies does not increase the spectrum of MFS substantially

 

2.  Measurement in CSF offers no additional value over serum

 

3.  Although ON (optic neuritis) can occur as part of the MFS, ISOLATED ON is NOT part of the MFS spectrum

 

4.  In acute opthalmoplegia, only 1/21 had positive antibodies but the antibodies occurred in 1/5 cases of AO of unknown etiology; therefore, the antibody may be useful as part of the evaluation of AO.  The cases with known etiology include diabetes, Tolosa Hunt and opsoclonus myoclonus

 

5. Low serum titers occur in several disorders and are markers of nonspecific damage to ocular motor nerve sheaths, while high concentrations are specific for MFS

 

6. IgG is the most relevant isotype antibody relevant for MFS, and GanglioCombi mixed IgM/IgG correlates well which makes it a viable alternative

code for chronic management labs

Z79.899

Froin's syndrome

CSF showing high protein, xanthochromia and hypercoagulation of CSF is pathognomonic and it can occur with blockage of CSF by a spinal cord mass or meningeal irritation from meningitis.

Orthostatic tremor - pearls

Hassan A, Ahlskog AE, Matsumotos JY.  Orthostatic tremor: clinical, electrophysiologic and treatment findings in 184 patients.  Neurology 2016; 86: 458-464.

The article is a Mayo series of 184 patients seen over 37 years. 

Definition: lower body tremor activated on standing, absent when seated or lying, improved by walking or leaning.  Patients report leg shaking, unsteadiness and imbalance.  Electrophysiologic findings are unique:  a 13-18 hz tremor of lower limbs or trunk. 

Demographics:  64 percent were female, mean age 59 years, (range 13-88) .  One hundred percent reported symptoms only when standing and absent while seated.  Descriptions included "imbalance, unsteadiness, weakness, 'funny feeling,' 'jelly legs,' leg tightness, pain, tremor, shakiness, or quivering.  Sixty percent of cases included the arms.  24 percent had falls.  28 percent had other types of tremors included ET, which could be associated with a response to alcohol.  Other associated tremors included head tremor  (1), handwriting tremor (2), functional (1), jaw tremor (1).  Forty percent had other neurologic diseases including Parkinson's and many others, degenerative or otherwise.  Nine patients had a family history of orthostatic tremor. 

Medication responsiveness occurred in 139 patients.  Sixty seven percent of medications prescribed did not demonstrate benefit.  The most efficacious was benzodiazepines, especially clonazepam, with 48 percent of patients so treated showing moderate or marked benefit.  Thirty three percent of patients given gabapentin showed mild or moderate benefit, with lower responses to valproate, primidone, levodopa (only 1/33 responding), and no benefit from anxiolytics or antidepressants.  The responsiveness to clonazepam diminished over time , and of those only a few, 16 got benefit from another drug, including gabapentin, valproic acid, propranolol, pramipexole, bromazepam, primidone, carbi-levodopa, and pregabalin.  Three patients underwent DBS and improved.

There was a high personal anf family history of PD (8.9 and 10.7 percent). 

EMG is easy and pathognomonic.  MRI's often show various types of white matter disease and occasional meningiomas.

Pellagra and spinal myoclonus

Park K, Oeda T, Sawada H. A case of alcoholic pellegra encephalopathy presenting with spinal myoclonus.  Neurology Clinical Practice 5; 472-3.

 

The authors present a case of alcoholic pellagra  with confusion and myoclonus responding dramatically to administration of niacin1500 mg per day starting 16 days after admission.  Essential points include:

 

1. Pellagra is rare in US but not in alcoholics

2. Dermatitis may be subtle and not appreciated

3.  Thiamine and niacin levels may be normal

4.  Thiamine may cause worsening due to increased demand for niacin

5.  Myoclonus in context is important to diagnosis, often stimulus sensitive

6.  Severe sensory ataxia, incontinence and dysautonomia also occur and improve with treatment

 

the 4 D's of pellagra, again, are , diarrhea, dementia, dermatitis and death

Additional pearl-- hamsters exposed to niacin deficiency (corn maize diet) cannibalize their young-- cite Current Nature ?

Scurvy and Neurologic disease

Meisal K, Daggubati S,Josephson SA. .  Scurvy in the 21st century?  Vitamin C deficiency presenting to the neurologist.  Neurol Clin Prac 2015; 5:491-493.

 

Authors present a series of cases with vitamin C deficiency and review some of the neuro manifestations and non neuro manifestations, ; the former are not widely known. 

 

Patients with deficiency were caused by various other causes,including autism, poor status without access to produce, usually rural, were not alcohol users, had measurable low vitamin C levels.  Gingival hyperplasia, rash and bleeding were non neurologic manifestations. People bruised,especially on their thighs, Some had other nutritional diseases..  Pain, achiness and weight loss are expected.

 

Neuro manifestations included positional tremor, neuralgias100 %), focal weakness (50 %)  including footdrop and scapular winging, normal MRI's, long tract signs including hyperreflexia and plantar extensors, fatigue, trouble concentrating, headache, anxiety, and imbalance.

 

Patients recovered dramatically with treatment.

Malignant subtypes of Parkinsons

JAMA Neurology august 2015
Importance  There is increasing evidence that Parkinson disease (PD) is heterogeneous in its clinical presentation and prognosis. Defining subtypes of PD is needed to better understand underlying mechanisms, predict disease course, and eventually design more efficient personalized management strategies.
Objectives  To identify clinical subtypes of PD, compare the prognosis and progression rate between PD phenotypes, and compare the ability to predict prognosis in our subtypes and those from previously published clustering solutions.
Design, Setting, and Participants  Prospective cohort study. The cohorts were from 2 movement disorders clinics in Montreal, Quebec, Canada (patients were enrolled during the period from 2005 to 2013). A total of 113 patients with idiopathic PD were enrolled. A comprehensive spectrum of motor and nonmotor features (motor severity, motor complications, motor subtypes, quantitative motor tests, autonomic and psychiatric manifestations, olfaction, color vision, sleep parameters, and neurocognitive testing) were assessed at baseline. After a mean follow-up time of 4.5 years, 76 patients were reassessed. In addition to reanalysis of baseline variables, a global composite outcome was created by merging standardized scores for motor symptoms, motor signs, cognitive function, and other nonmotor manifestations.
Main Outcomes and Measures  Changes in the quintiles of the global composite outcome and its components were compared between different subtypes.
Results  The best cluster solution found was based on orthostatic hypotension, mild cognitive impairment, rapid eye movement sleep behavior disorder (RBD), depression, anxiety, and Unified Parkinson’s Disease Rating Scale Part II and Part III scores at baseline. Three subtypes were defined as mainly motor/slow progression, diffuse/malignant, and intermediate. Despite similar age and disease duration, patients with the diffuse/malignant phenotype were more likely to have mild cognitive impairment, orthostatic hypotension, and RBD at baseline, and at prospective follow-up, they showed a more rapid progression in cognition (odds ratio [OR], 8.7 [95% CI, 4.0-18.7]; P < .001), other nonmotor symptoms (OR, 10.0 [95% CI, 4.3-23.2]; P < .001), motor signs (OR, 4.1 [95% CI, 1.8-9.1]; P = .001), motor symptoms (OR, 2.9 [95% CI, 1.3-6.2]; P < .01), and the global composite outcome (OR, 8.0 [95% CI, 3.7-17.7]; P < .001).
Conclusions and Relevance  It is recommended to screen patients with PD for mild cognitive impairment, orthostatic hypotension, and RBD even at baseline visits. These nonmotor features identify a diffuse/malignant subgroup of patients with PD for whom the most rapid progression rate could be expected.

View Original Article