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<b>Now let's talk about some</b>
<b>of the paraneoplastic</b>
<b>or paraproteinemic neuropathies.</b>
<b>We see two broad</b>
<b>categories of cancer</b>
<b>or cancer-associated conditions</b>
<b>that can cause neuropathy.</b>
<b>The first are the</b>
<b>paraproteinemias.</b>
<b>These are disorders</b>
<b>like multiple myeloma,</b>
<b>monoclonal gammopathy of</b>
<b>undetermined significance,</b>
<b>Waldenstrom's macroglobulinemia,</b>
<b>and lymphoid or lymphomatous neuropathy</b>
<b>and that is infiltration of the nerves</b>
<b>from lymphoma or neurolymphomatosis.</b>
<b>In addition,</b>
<b>we can see paraneoplastic etiologies</b>
<b>where there is an underlying cancer</b>
<b>that is revved up the immune system</b>
<b>and the immune system</b>
<b>is attacking the nerves.</b>
<b>And the most common and classic</b>
<b>presentation is anti-Hu antibody syndrome,</b>
<b>which presents with a prominent</b>
<b>sensory ganglionopathy.</b>
<b>Let's talk about a couple</b>
<b>of these conditions</b>
<b>and start with anti-Hu</b>
<b>antibody polyneuropathy.</b>
<b>This is a sensory</b>
<b>predominant polyneuropathy</b>
<b>associated with systemic</b>
<b>anti-Hu antibodies,</b>
<b>and it results in a</b>
<b>sensory ganglionapathy.</b>
<b>Patients have predominant</b>
<b>sensory symptoms</b>
<b>in the absence of</b>
<b>motor symptoms.</b>
<b>Importantly, the sensory afferents</b>
<b>are important in the reflex arc.</b>
<b>So we do see reduced or</b>
<b>absent deep tendon reflexes</b>
<b>with a predominance of sensory</b>
<b>abnormalities with normal motor strength.</b>
<b>Some important presentations of</b>
<b>anti-Hu antibody polyneuropathy</b>
<b>include a pure sensory</b>
<b>ganglionopathy,</b>
<b>this is associated with</b>
<b>small cell lung cancer,</b>
<b>somewhere around 25% of patients</b>
<b>with small cell lung cancer</b>
<b>will develop anti-Hu antibodies,</b>
<b>and in a subset of those patients</b>
<b>they will become pathologic</b>
<b>and result in damage to the sensory</b>
<b>ganglion the dorsal root ganglion,</b>
<b>presenting with prominent</b>
<b>vibration proprioception</b>
<b>and in some cases pain and</b>
<b>temperature dysfunction</b>
<b>as well as light touch a</b>
<b>sensory ganglionopathy.</b>
<b>The second presentation is a</b>
<b>sensorimotor polyneuropathy.</b>
<b>Patients have sensory predominance</b>
<b>but there is associated motor findings</b>
<b>on EMG nerve conduction</b>
<b>study or on clinical exam.</b>
<b>And then the last,</b>
<b>we can see a sensory ataxic neuropathy</b>
<b>where patients have</b>
<b>severe proprioceptive loss</b>
<b>to the point that there is</b>
<b>prominent sensory ataxia.</b>
<b>They do not know where</b>
<b>their fingers are in space,</b>
<b>a sensory choreoathetosis, where the</b>
<b>fingers will move on their own can occur</b>
<b>and significant</b>
<b>difficulty with dysmetria</b>
<b>and coordination of both the appendicular</b>
<b>function and truncal coordination.</b>
<b>To make a diagnosis of anti-Hu</b>
<b>antibody polyneuropathy</b>
<b>and other paraneoplastic</b>
<b>polyneuropathies,</b>
<b>the LP is critically important.</b>
<b>We're looking for</b>
<b>evidence of inflammation,</b>
<b>elevated protein often with</b>
<b>normal cell counts no pleocytosis.</b>
<b>And we do antibody testing looking</b>
<b>for those paraneoplastic antibodies,</b>
<b>including the anti-Hu antibody.</b>
<b>To look for</b>
<b>paraneoplastic antibodies,</b>
<b>we often start our diagnostic</b>
<b>investigation in the serum.</b>
<b>These are antibodies,</b>
<b>they circulate around in the serum</b>
<b>before gaining</b>
<b>access to the nerve,</b>
<b>the spinal fluid or other</b>
<b>parts of the nervous system.</b>
<b>But we can do CSF testing, particularly</b>
<b>when serum testing is negative.</b>
<b>And the presence in the CSF</b>
<b>of a paraneoplastic antibody</b>
<b>is essentially diagnostic of an</b>
<b>underlying pathologic process.</b>
<b>When we treat these patients,</b>
<b>we're managing the immune system.</b>
<b>So there's two parts in managing</b>
<b>a paraneoplastic process.</b>
<b>The first is to treat</b>
<b>the underlying cancer,</b>
<b>that's the nidus for revving</b>
<b>up the immune system,</b>
<b>the activation of</b>
<b>the immune system.</b>
<b>And by treating the cancer, we remove</b>
<b>that stimulus of the immune system.</b>
<b>While patients are undergoing cancer</b>
<b>treatment or at the initial presentation</b>
<b>or in patients where the</b>
<b>cancer is unable to be treated.</b>
<b>We think about immunomodulating</b>
<b>therapy suppressing the immune system</b>
<b>so that the immune response and</b>
<b>attack on the nerves is subsided.</b>
<b>IV steroids methylprednisolone as</b>
<b>well as IVIG and plasmapheresis</b>
<b>can be used in those settings.</b>
<b>Now let's talk about some of the</b>
<b>paraproteinemic polyneuropathies.</b>
<b>These are polyneuropathies occurring</b>
<b>in patients with a paraproteinemia.</b>
<b>We see neuropathy with an increased M-spike</b>
<b>or an increased in a monoclonal paraprotein</b>
<b>that can occur in multiple myeloma</b>
<b>which is a plasma cell disorder</b>
<b>with monoclonal gammopathy</b>
<b>of undetermined significance,</b>
<b>or Waldenstrom's</b>
<b>macroglobulinemia.</b>
<b>In these patients, we're looking for</b>
<b>an elevation in a pair of protein</b>
<b>or an M-spike either</b>
<b>in the blood or urine,</b>
<b>which would warrant further hematologic</b>
<b>evaluation in these patients.</b>
<b>Neuropathy is a common</b>
<b>presenting symptom.</b>
<b>And so sometimes neuropathy is the first</b>
<b>sign of an underlying paraproteinemia</b>
<b>that would require further evaluation</b>
<b>and potentially management.</b>
<b>The etiology and pathophysiology</b>
<b>of the paraproteinemic</b>
<b>neuropathies is increased protein.</b>
<b>As a result of this</b>
<b>increase in immunoglobulins,</b>
<b>which is composed of a</b>
<b>heavy and light chain,</b>
<b>we see increased protein</b>
<b>circulating in the blood.</b>
<b>This can cause deposition in small vascular</b>
<b>beds, we can see kidney dysfunction,</b>
<b>as well as deposition of</b>
<b>proteins in the nervorum,</b>
<b>the small vascular</b>
<b>beds around the nerve,</b>
<b>and this can result in</b>
<b>neuropathy in these patients.</b>
<b>Though a differential diagnosis</b>
<b>for a paraproteinemic neuropathy</b>
<b>includes POEMS:</b>
<b>Polyneuropathy, Endocrinopathy,</b>
<b>Ophthalmoplegia,</b>
<b>M-spike and skin findings,</b>
<b>that's a patient with</b>
<b>neuropathy with an M-spike.</b>
<b>But the presence of these other organ</b>
<b>involvements would point towards POEMS,</b>
<b>as opposed to an underlying</b>
<b>multiple myeloma or MGUS.</b>
<b>Neuropathy with</b>
<b>M-spike can be seen.</b>
<b>Lymphomatous neuropathy</b>
<b>is a neuropathic condition</b>
<b>where we can see an M-spike and</b>
<b>maybe similar to Waldenstrom's</b>
<b>as well as amyloid</b>
<b>neuropathy, cryoglobulinemia.</b>
<b>These are all conditions</b>
<b>where patients present</b>
<b>with neuropathy in</b>
<b>association with M-spike</b>
<b>and our diagnostic work up should</b>
<b>include evaluation of these conditions.</b>