Sjogren's Pearls

J. Birnbaum. Peripheral nervous system manifestations of Sjogren syndrome: clinical patterns, diagnostic paradigms, etiopathogenesis, and therapeutic strategies. The Neurologist 2010; 16:5:287 -- 297 .

1.Syndromes that can cause sicca symptoms and which should be typically excluded, include hepatitis B or hepatitis C, HIV, sarcoidosis, and a history of radiation to either the header the neck.

2. 30% to 50% of patients have negative auto antibodies and require a lip biopsy for diagnosis.

3.  Sensory ganglionapathy : aka sensory  neuronopathy is dramatic with isolated or disproportionate impairment of kinesthetic awareness, with profound handicap of proprioception, even affecting the larger joints. Sensory deafferentation can cause patients to become wheelchair-bound, or have pseudoathetoid movements which may be misdiagnosed as a movement disorder. The most common presentation is distal dysesthesias.  Differential diagnosis includes paraneoplastic syndromes, Bickerstaff brainstem encephalitis, and effect of drugs for example, cisplatin and pyridoxine. Nerve conduction studies typically absent sensory nerve action potential(snaps) and preserved compound motor action potentials (cmap). T2 hyper intensities in the dorsal spinal cord are described. Response to I VIG is inconsistent.

4.  Small fiber neuropathy: the cardinal feature can be excruciating burning pain. There is disproportionate or selective impairment in pinprick and temperature with preserved vibratory sense and proprioception. The onset is subacute or chronic usually. The differential diagnosis includes diabetes, amyloidosis, chemotherapy and other medications, genetic syndromes (i.e. Fabry's) and complications from HIV treatment.

5.  Patients with findings of small fiber dysfunction disproportionally affecting the proximal extremities, torso or face in unorthodox patterns may have Sjogren's. Patients may also have classic length dependent symptoms.

6.   Sjogrens and vasculitis: patients with mononeuritis multiplex should be evaluated for cryoglobulinemia especially with high titer rheumatoid factor, with disproportionate C-4 hypo-complementemia, or normal C-3. Small vessel vasculitis and low levels of C-4 complement in Sjogren's space placed the patient at 6 to 40.  fold risk for non-Hodgkin's lymphoma. Therefore the development of systemic features such as fever or weight loss merit close scrutiny. Nerve or muscle biopsy showing vasculitis more likely responds to immunosuppressive therapy. Mori described patients with axonal MMN who also had cranial neuropathies. The most common is trigeminal neuropathy  which may be indolent, progressive, or bilateral. The unifying feature may be ganglionapathy.  Facial nerve also may be affected. Acute cranial neuropathy plus rapid multiple mono neuropathies may prompt concern for vasculitis.

7. Demyelinating neuropathies are rare but may be noted subclinically. EMG may know isolated prolonged F. waves.
8. Autonomic features are seen in 50% of Sjogren's patients. Inquire about urinary frequency or hesitancy, erectile dysfunction, increased or decreased sweating, orthostatic or temperature intolerance, constipation or increased bowel movements. Adie's pupil , space orthostatic hypotension, and abnormal sweating occurs in 57, 40, and 70% of patients with sensory neuronopathy respectively.

9. Anti-nicotinic ganglionic receptor antibody role is under investigation in Sjogren's. This antibody differs from the anti-muscarinic receptor antibody seen in myasthenia gravis.

10. Inflammatory myopathies occur only in 1 to 2%. Myalgias  may be caused by autoimmune thyroid disease, vitamin D. deficiency, or fibromyalgia. Always assess vitamin D level. Vitamin D may be low due to malabsorption, bacterial deconjugation of bile acids due to gastric motility seen in autonomic neuropathies, type one renal tubular acidosis or coexisting celiac sprue.

Clinical utility of seropositive voltage gated calcium chanell complex antibody

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.

Clinical spectrum of voltage gated potassium channel (VGKC) autoimmunity

Tan KM, Lennon et al. Neurology 2008; 70:1883-1890. 

80 patients were found, 71 with clinical information available.  Mean age 65.

Neurologic symptoms were subacute or chronic including

1.  cognitive impairment 71 %-- see below

2.  seizures 58 %-- several types

3.  dysautonomia 33 %

4.  myoclonus  29 %

5.  dyssomnia 26 %

6.  peripheral nerve dysfunction 25 %

7.  EPS 21 %

8.  brainstem/cranial nerve dysfunction 19 %-- vision loss/blurred vision, diplopia, dysarthria, hemifacial spasm, facial numbness, anosmia.

9.  hypothalamic involvement-- 38 %-- hyponatremia (36 %) , hyperphagia, (8%) 

Common misdiagnosis was CJD (14 %)..  Other misdiagnoses:  viral encephalitis, recurrent TGA, generalized anxiety disorder, conversion disorder.

Associated tumors (paraneoplastic) 33 % confirmed histologically

carcinoma 18, adenoma 5, thymoma1, hematologic 3.

Associations

hyponatremia  36 %

other organ specific autoantibodies 49 %

coexisting autoimmune disorder 33 % (thyroiditis, DM)

34/38 responded to immunotherapy, half "vigorously" so.

Classic reports of association:

1.  Morvan's syndrome

2,  acquired neuromyotonia

3.  epilepsy

4.  limbic encephalitis

5.  dysatuonomia

6.  lung carcinoma
7. FACIAL BRACHIAL DYSTONIC SEIZURE

Cognitive presentation:

1.  frontosubcortical (personaltiy change, disinhibition,  executive dysfunction) 13 %

2.  Visual hallucination (10 %)

3.  Depression or agitation (13 %)

Treatment of orthostatic hypotension in Parkinson's disease

Source: Neurology 2009 supplement cited above, p.S83

 

1. Consider a role for medication, including selegeline, levodopa, DA agonists and MAO inhibitors.

2.  Increase sodium intake, especially in daytime.

3.  Avoid lying flat which leads to release of renin. Elevate HOB and legs.

4.  Postprandial hypotension can be avoided with small meals, with low carbohydrate intake and avoiding alcohol

5.  Caffeine with breakfast can be helpful

6.  Heat related vasodilatation, vasovagal activities (straining at stool, playing wind instruments, singing all can be considered/limited if applicable.

7.  Isometric exercise especially swimming

8.  Avoid knee high TEDS, consider waist high Jobst stockings or abdominal binders.

 

Medication:

1. Florinef up to 0.5 (start with 0.1 mg).

2. DDAVP 5-40 ug intranasally at bedtime can be tried.  Monitor Na+ in first 4-5 days of treatment and monthly thereafter.  It can cause a severe and life threatening hyponatremia.

3.  Midodrine, start at 2.5 mg per day, do not go above 10 tid, and do not give at bedtime.

4. Erythropoietin 4,000 units biw especially if anemic also.

5.  End of dose sweating can be an "off" phenomenon and can eb treated with more dopamine.

Treating constipation in Parkinson's disease, and urinary problems

Regimen suggested in Neurology 72:21:2009 S4 pp S80-81.

Bowel:

Management consists of dietary changes, exercises and pharmacotherapy.

1.  Dietary changes-- Increase bulk, and soften stool.  Drink 6-8 glasses of water per day.  Increase fiber, decrease baked goods.  @ meals should have high fiber raw vegetables.  Oat bran can be used.  Exercise, including walking, is encouraged. 

 

If stools remain hard, docusate, or lactulose 10-20 grams per day can be used.  Miraelx (otc) can be used.  Patients should be educated about possibble delayed onset and reminded to do the things in paragraph one above. 

 

Third line is milk of magnesia and other laxatives or enemas.  Apomorphine rescue therapy can be used. 

 

Urinary:

Nocturia is earliest problem, then urgency, frequency and hesitancy.  Consider detrusor hyperreflexia v. incomplete/delayed relaxation of the pelvic floor.  Supine hypertension can also cause pressure natriuresis.  Incomplete emptying can be an "off" symptom. UTI should be considered if any change occurs in symptoms. 

 

Avoid nighttime water drinking.  Try Detrol or Ditropan.  Midodrine can worsen symptoms due to increasing sphincter tone.  Diazepan, baclofen or dantrolene can be used to relax sphincter tone occassionally. 

 

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Diagnosis of parkinsonism

Classic criteria indicate the triad of resting tremor, akinesia/bradykinesia, and cogwheel rigidity, with two of three being associated with the diagnosis of Parkinson's disease.  At the London Brain bank, the diagnosis was not confirmed in 24 of 100 patients with these premorbid clinical symptoms (Hughes et al., JNNP 1992).  The alternative triad of parkinsonism, assymetry, and response to levodopa correctly identified 98 % in 73 patients reported in a subsequent trial (Hughes et al., Brain 2002) and was therefore considered better. 

 

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Optic atrophy helpful hints

 

from AAN 2010 course

differentiate pallor from atrophy

 

segmental patterns

signs of prior disc-- swelling high water marks and gliosis, fuzzy edges,

collateral venous vessels-- retinal choroid collaterals, AION or post pappilledeme

macular exudates pretty "fireworks" around macula

attenuated arterioles-- "ghost vessels" with  gliosis

 

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mimics of optic atrophy

from aan course 2010

 

physiologic temporal pallor

aphakia/pseudoaphakia-- after take out lenses after cataract surgery

anemia

myopic discs

optic nerve hypoplasia

myelinated optic nerve fiber layers

 

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neuropthy downloads UTAH

http://library.med.utah.edu/NOVEL/

 

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