Wilsons Ds Penicillamine and Zinc meals relationship

Penicillamine has to be given one hr before or two hr after meals. When giving both Penicillamine and Zinc to the same patient, we can give Penicillamine before meals and Zinc after meals. [Or - give Zinc one hour before meals and Penicillamine two hours after meals]

MRI sensitivity for spinal vascular malformations

The more specific findings of intradural flow voids on T2-weighted images, and/or serpentine enhancement on MRA and T1 images, are seen in 85 to 90 percent of patients.
From: Uptodate

Sensory Neuronopathies

http://neuromuscular.wustl.edu/antibody/sneuron.html

Causes of Sensory Neuronopathies

1. Immune mediated - paraneoplastic (anti Hu), Sjogren's, acute sensory neuronopathy
2. Idiopathic - pan-sensory, small fiber, CANVAS
3. Drugs - Pyridoxine, cisplatin, doxorubicin
4. Hereditary
5. Localized - zoster

NB: CANVAS = Cerebellar ataxia, Neuropathy, Vestibular areflexia syndrome

Hereditary Motor Syndromes with Multisystem Involvement

http://neuromuscular.wustl.edu/synmot.html

Hexosaminidase A (Late onset GM2 Gangliosidosis - Tay Sach's disease)
Motor neuropathy +/- CNS (LMN dominant)
Cramps, paresthesias at onset
Symmetric proximal > distal weakness
Fasciculations
+/- CNS involvement - spasticity, ataxia, dementia, dystonia

Adult onset Polyglucosan body disease
CNS + Neuropathy
Dementia in 2/3rd
Cord - spasticity
Nerve - Motor and sensory

Cranial Nerve involvement in CIDP

From Uptodate: 10 to 20% in the classic CIDP

Another cause for myeloneuropathy

Copper deficiency can cause myeloneuropathy. Zinc excess or malabsorption syndrome are the common cause for same. Denture creams containing excess zinc can cause copper deficiency.
In fact zinc is used in Wilson's disease because of its ability to induce metallothionein, which binds copper and reduces its absorption.
Clioquinol, the cause for SMON (myeloneuropathy with optic nerve involvement), is an avid chelator. It has been used in acrodermatitis enteropathica, a childhood disease due to a hereditary defect in zinc transport. Clioquinol binds zinc and improves the transport into the circulation.
From:
Schaumburg H. Copper deficiency myeloneuropathy: A clue to clioquinol-induced subacute myelo-optic neuropathy? Neurology 2008; Vol 71, Issue 9

Dermatomyositis and polymyositis

DM - Humoral immunity directed against vessels, children + adults, CK can be normal
PM - Cytotoxic T cell mediated immune activation against muscle membrane, mostly adults, abnormal CK
Bradley 5th Ed 2008

Anemia WHO Cut offs and grading (Wiki)

 WHO's Hemoglobin thresholds used to define anemia  (1 g/dL = 0.6206 mmol/L)
Age or gender group                     Hb threshold (g/dl)      Hb threshold (mmol/l)
Children (0.5–5.0 yrs)                  11.0                            6.8
Children (5–12 yrs)                      11.5                            7.1
Teens (12–15 yrs)                        12.0                            7.4
Women, non-pregnant (>15yrs)    12.0                            7.4
Women, pregnant                         11.0                            6.8
Men (>15yrs)                               13.0                            8.1

WHO Grading of anemia:

• Grade 1 (Mild Anemia): 10 g/dl - cutoff point for ages
• Grade 2 (Moderate Anemia): 7-10 g/dl
• Grade 3 (Severe Anemia): below 7 g/dl

SSRI and MAO-BI

SSRI given along with MAO-BI can result in Serotonin syndrome.

PMP22

Duplication results in HMSN1
Mutation, deletion in HNPP
Done in Delhi SGRH

Rasagiline

Selective MAO-B irreversible inhibitor.

Adv over Selegeline - OD dose, milder S/E, non-amphetamine metabolites

ADAGIO trial suggested neuroprotective at 1mg, but findings did not hold at 2mg/day.

Knapsack palsy

Typically Long thoracic nerve with serratus anterior palsy

Posterior interosseus syndrome

Finger drop without wrist drop (differentiates it from radial palsy due to compression in spiral groove)

VEGF and Neuropathy

Serum VEGF levels in POEMS syndrome and in immune-mediated neuropathies.
Nobile-Orazio E - Neurology - 17-MAR-2009; 72(11): 1024-6

This study confirms that serum VEGF levels are constantly increased in patients with POEMS syndrome, if only markedly increased levels (>3,489 pg/mL in our system) were specifically associated with this syndrome. VEGF levels were also moderately, though significantly, increased in patients with immune-mediated neuropathies (excluding MMN) compared to other PN and were significantly associated with immune-mediated neuropathies. These results indicate that moderately increased VEGF levels should be interpreted cautiously in the diagnosis of POEMS, whereas once this diagnosis is excluded, they may help in identifying an immune-mediated neuropathy.

VEGF is a potent multifunctional cytokine inducing angiogenesis and microvascular hyperpermeability, which may explain many of the symptoms of POEMS. Its possible pathogenetic role in POEMS is supported by its highly increased levels in this syndrome and their decrease concomitant to clinical improvement. The origin and pathogenetic role of VEGF in immune-mediated neuropathies remains unclear. Its presence in inflammatory neuropathies such as CIDP and GBS and in vasculitic neuropathy a possible relation with vascular involvement whereas its increase in PN+IgM where no inflammation or vascular involvement has been reported suggests that it might be related to the immune response itself. Whether this increase may also have a role in the progression of these neuropathies remains to be elucidated.

POEMS Syndrome

From
Bradley: Neurology in Clinical Practice, 5th ed.

Osteosclerotic Myeloma and POEMS Syndrome
Osteosclerotic myeloma occurs in less than 3% of all patients with myeloma, but 85% of these patients present with an associated peripheral neuropathy. In this disorder the plasma cell proliferationoccurs as single or multiple plasmacytomas that manifest as sclerotic bone lesions.

The neuropathy of osteosclerotic myeloma is different from that associated with multiple myeloma in several aspects: It occurs at an earlier age and mostly in men; it is a demyelinating, predominantly motor neuropathy with slow motor NCVs and elevated CSF protein levels, usually in excess of 100 mg/dL; an M protein is found in 90% of cases and is virtually always composed of λ light chains associated with IgG and IgA heavy chains; it responds to irradiation or excision of the isolated plasmacytoma; and it is associated with systemic manifestations referred to as Crow-Fukase, or POEMS, syndrome.

To reiterate, POEMS is the acronym for polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes, facilitating recognition of the most constant features of this multisystem syndrome.

The neuropathy of osteosclerotic myeloma bears a striking resemblance to CIDP with symmetrical proximal and dis-tal weakness with variable sensory loss. Cranial nerves are spared except for occasional cases of papilledema. The clinical and electrophysiological similarities between this condition and CIDP emphasize the need to screen for anoccult M protein and sclerotic bone lesions in all adult patients presenting with an acquired demyelinating neuropathy.
The skeletal lesions can be single or multiple and tend to involve the axial skeleton; the majority of lesions occur in the spine, pelvis, and ribs. Their radiographical appearance varies from dense ivory to mixed sclerotic and lytic lesions with a sclerotic rim. Radioisotope scans are less sensitive than radiographical skeletal surveys in detecting the lesions. Open biopsy is usually necessary to confirm the presenceof an isolated plasmacytoma.

Most patients develop one or more of the multisystem manifestations of the POEMS syndrome . Hepatosplenomegaly is often encountered. Gynecomastia and impotence in men, secondary amenorrhea in women, diabetes mellitus, and hypothyroidism are the most common endocrinopathies. Hyperpigmentation, hypertrichosis, diffuse skin thickening, hemangiomas, and white nail beds are dermatological features. Pitting edema of the lower limbs, ascites, pleural effusions, and clubbing of the fingers are other signs. Approximately one fourth of patients with POEMS syndrome have no associated bone lesions. Some of these patients have Castleman's syndrome (a nonmalignant form of angiofollicular lymphadenopathy), and others have a plasma cell dyscrasia restricted to the lymphoreticular system.

The pathogenesis of this multiorgan disorder is poorly understood. The associated plasma cell dyscrasia seems to play a crucial role, as clinical improvement follows the disappearance of the monoclonal proteins. Elevated levels of proinflammatory cytokines, such as TNF-α, interleukins, and vascular endothelial growth factor (VEGF) have been implicated in the multisystem manifestations. The markedly increased serum VEGF level in POEMS is not observed in other demyelinating neuropathies. The high serum level is usually decreased dramatically following successful treatment, implying a major role played by VEGF in the development of the syndrome and neuropathy.

The importance of recognizing this rare syndrome lies in its potential for treatment. Patients with solitary lesions are treated with tumoricidal irradiation, complete surgical extirpation, or both. Patients with multiple bone lesions receive radiation combined with prednisone and melphalan. High-dose chemotherapy with autologous blood stem cell support is another option for patients with multifocal bone lesions or diffuse bone marrow plasmacytic infiltration. Substantial improvement of both neurological and systemic features is seen in some patients, but the response may take many months.