Small Vessel Vasculitis and Mononeuropathies in Diabetes
Small Vessel Vasculitis and Mononeuropathies in Diabetes
Our patient presented with progressive mononeuropathy multiplex, dysautonomia and cognitive decline, with a known history of diabetes mellitus that was suboptimally controlled. The electrodiagnostic studies and nerve biopsy were consistent with chronic axonal mononeuritis multiplex with ongoing nerve degeneration. Although diabetic radiculoplexus neuropathy is a rare cause of brachial diplegia, this clinical sign was attributed to mononeuropathy multiplex rather than bilateral brachial plexopathies, cervical radiculopathies or anterior horn cell disease based on the electrodiagnostic data. Distinguishing between brachial plexopathies and multiple mononeuropathies by electrodiagnostic testing can be challenging. The distinction depends on recognizing significant variability within individual nerves and nerves derived from the same trunk.
Our patient had severe orthostatic hypotension, with cardiovascular sympathetic α- and β-adrenergic dysfunction. Autonomic neuropathy is a well-recognized complication of diabetes, and may be found in isolation (preclinical or clinical) or in combination with diabetic polyneuropathy or other non-neurologic complications of diabetes. Up to 20% of diabetic patients may have cardiovascular autonomic dysfunction. However, an autonomic neuropathy may also occur in patients with connective tissue disorders and vasculitis. Studies have shown a variable range (24 to 100%) of sympathetic and parasympathetic dysfunction in patients with autoimmune diseases. In some cases, the autonomic neuropathy may be subclinical, or present as an initial clinical manifestation.
Finally, our patient also had moderate cognitive impairment on initial clinical presentation, involving frontal, parietal and temporal domains based on his MoCA data. A population-based study revealed that early onset, longer duration and greater severity of diabetes are associated with mild cognitive impairment. This cognitive decline was attributed to cerebral microvascular disease and subclinical infarctions. The rate of cognitive decline observed in our patient raised the possibility for an alternative etiology. Although elevated CSF protein may be seen in diabetics, the elevated intrathecal IgG synthesis further raised our suspicion for an inflammatory or immune-mediated etiology. Cognitive impairment has been described in patients with small vessel vasculitis.
A small study reported that up to 30% of patients with small vessel vasculitis developed subclinical mild cognitive impairment, with mild abstract reasoning loss and non-verbal memory impairment being common manifestations. Cognitive changes may be associated with an inflammatory encephalopathy. In support of this, frontal executive disorder, attention deficit and affective disorders have been described in Sjögren's syndrome. Recognizing clinical features that may support vasculitis rather than diabetic vasculopathy is important, as adjunctive immunosuppressant therapy would be required in the former and may worsen glycemic control without clinical benefit in the latter.
An extensive evaluation for systemic causes of vasculitis was unrevealing. Although peripheral nerve biopsies are invasive, this procedure is indicated when there is a high clinical suspicion for a non-systemic vasculitic neuropathy, in atypical diabetic neuropathies or suspected additional causes of neuropathy in diabetics. Our patient met these criteria and the superficial radial biopsy confirmed the diagnosis of small vessel vasculitis; a diagnosis that significantly altered clinical management. Demonstrable clinical improvement was observed with chronic immunosuppressant therapy (over at least a year), in conjunction with adjunctive glycemic control and supportive pharmacotherapies and rehabilitation.
Discussion
Our patient presented with progressive mononeuropathy multiplex, dysautonomia and cognitive decline, with a known history of diabetes mellitus that was suboptimally controlled. The electrodiagnostic studies and nerve biopsy were consistent with chronic axonal mononeuritis multiplex with ongoing nerve degeneration. Although diabetic radiculoplexus neuropathy is a rare cause of brachial diplegia, this clinical sign was attributed to mononeuropathy multiplex rather than bilateral brachial plexopathies, cervical radiculopathies or anterior horn cell disease based on the electrodiagnostic data. Distinguishing between brachial plexopathies and multiple mononeuropathies by electrodiagnostic testing can be challenging. The distinction depends on recognizing significant variability within individual nerves and nerves derived from the same trunk.
Our patient had severe orthostatic hypotension, with cardiovascular sympathetic α- and β-adrenergic dysfunction. Autonomic neuropathy is a well-recognized complication of diabetes, and may be found in isolation (preclinical or clinical) or in combination with diabetic polyneuropathy or other non-neurologic complications of diabetes. Up to 20% of diabetic patients may have cardiovascular autonomic dysfunction. However, an autonomic neuropathy may also occur in patients with connective tissue disorders and vasculitis. Studies have shown a variable range (24 to 100%) of sympathetic and parasympathetic dysfunction in patients with autoimmune diseases. In some cases, the autonomic neuropathy may be subclinical, or present as an initial clinical manifestation.
Finally, our patient also had moderate cognitive impairment on initial clinical presentation, involving frontal, parietal and temporal domains based on his MoCA data. A population-based study revealed that early onset, longer duration and greater severity of diabetes are associated with mild cognitive impairment. This cognitive decline was attributed to cerebral microvascular disease and subclinical infarctions. The rate of cognitive decline observed in our patient raised the possibility for an alternative etiology. Although elevated CSF protein may be seen in diabetics, the elevated intrathecal IgG synthesis further raised our suspicion for an inflammatory or immune-mediated etiology. Cognitive impairment has been described in patients with small vessel vasculitis.
A small study reported that up to 30% of patients with small vessel vasculitis developed subclinical mild cognitive impairment, with mild abstract reasoning loss and non-verbal memory impairment being common manifestations. Cognitive changes may be associated with an inflammatory encephalopathy. In support of this, frontal executive disorder, attention deficit and affective disorders have been described in Sjögren's syndrome. Recognizing clinical features that may support vasculitis rather than diabetic vasculopathy is important, as adjunctive immunosuppressant therapy would be required in the former and may worsen glycemic control without clinical benefit in the latter.
An extensive evaluation for systemic causes of vasculitis was unrevealing. Although peripheral nerve biopsies are invasive, this procedure is indicated when there is a high clinical suspicion for a non-systemic vasculitic neuropathy, in atypical diabetic neuropathies or suspected additional causes of neuropathy in diabetics. Our patient met these criteria and the superficial radial biopsy confirmed the diagnosis of small vessel vasculitis; a diagnosis that significantly altered clinical management. Demonstrable clinical improvement was observed with chronic immunosuppressant therapy (over at least a year), in conjunction with adjunctive glycemic control and supportive pharmacotherapies and rehabilitation.
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