Diagnosis and reasoning

To the uninitiated, clinical neurology is perhaps one of the most difficult branches of medicine, given the amazing diversity of presentations; however, a solid knowledge of neuroanatomy combined with an analytical approach are often capable of unraveling even the trickiest of these puzzles. The patient in this case scenario is an excellent example in point. A glance at his history reveals the presence of sensory disturbances involving the right chest and abdomen; note also the presence of weakness of the right lower limb, suggesting at a motor lesion. He also complains of a rather interesting and unusual symptom - a bulge in his right abdomen which appears after meals. This could be a hernia; alternatively, it could be due to weak abdominal musculature. Examination reveals impairment of light touch from D4 to D10, and crude touch from D4 to the right knee; a lower motor neurone type weakness is also seen in the proximal right lower limb, while abdominal reflexes are absent. Interestingly enough, there is no evidence of a right-sided abdominal hernia or mass; an ultrasound scan confirms the absence of an anatomical lesion. Thus, muscular weakness seems to be the likely cause of the bulging. When the above signs and symptoms are considered together, they are most suggestive of a multifocal sensorimotor neuropathy; important etiologies presenting in this manner include diabetes mellitus, vasculitic syndromes, multifocal chronic inflammatory demyelinating polyneuropathy (CIDP), sarcoidosis, HIV/AIDS, and leprosy. However, HIV/AIDS is unlikely, as these patients typically display a relapsing and remitting disease course (rather than the progressive nature seen here). Leprosy is also unlikely, as nerve involvement is usually far more 'patchy'; furthermore, motor involvement in leprosy preferentially affects the small muscles of the hands and feet. Sarcoidosis is also less likely, as the neuropathy usually starts distally and then progresses proximally. Thus, considering the clinical findings, the key diagnoses remaining are diabetic neuropathy, multifocal CIDP, and vasculitis. The first step in his investigative workup should be confirmation that this is indeed a neuropathy and not a myelopathy (which can mimic these findings); however, contrast MRI imaging of the cervical, dorsal and lumbosacral spine excludes this possibility. The next step should be electrodiagnostic studies, aiming to determine whether the neuropathy is due to axon loss or demyelination; note that the pattern seen in this patient is suggestive of the former. Of the above listed differentials, diabetes mellitus and vasculitic syndromes are the main causes of axonal neuropathy; given his history of poorly controlled diabetes, the former becomes highly likely; note also that there are no clinical features suggestive of vasculitis, while his ESR and CRP are both within normal parameters. Thus, this is very likely diabetic thoracic radiculoneuropathy (DTRN) combined with a unilateral proximal radiculopathy of the right lower limb; this diagnosis provides a good explanation for the abdominal bulging after meals as well, as this is well known to occur in DTRN due to weakening of the abdominal muscles. Good analgesia is very important in his management, given that his quality of life is being adversely affected; the antiepileptic Gabapentin is a suitable choice in this regard. The centrally acting atypical opioid analgesic Tramadol can also be added for further relief. Note that carbamazepine, while effective, is not preferred as an analgesic agent now, due to the potential for adverse effects. Physical therapy with muscle strengthening exercises should be prescribed, given the weakness of the proximal lower limb and abdominal musculature.

Discussion

Neuropathies are the most common complication of diabetes mellitus, affecting up to half of all patients with the disease; these take on numerous forms, ranging from distal symmetric polyneuropathy to mononeuritis multiplex. Diabetic radiculoplexus neuropathies (DRPN) are one of the aforementioned forms, typically presenting subacutely with pain followed by weakness, and mainly affecting patients with mild, uncontrolled diabetes. There are 3 main types of DRPN, which may occur singly, or in combination: - Diabetic cervical radiculoplexus neuropathy - Diabetic thoracic radiculoneuropathy - Diabetic lumbosacral radiculoplexus neuropathy The remainder of this monograph focuses on diabetic thoracic radiculoneuropathy (DTRN) alone; however, that much of the following applies to the other forms as well. Patients with DTRN typically present with severe pain and dysesthesia along the chest, trunk or abdominal wall; multiple dermatomes may be involved, sometimes bilaterally. The affected muscles may become weak, resulting in outpouching of abdominal wall; this may mimic an abdominal hernia. These patients may also experience significant weight loss. Given the constellation of potentially alarming symptoms encountered in the condition, these individuals are often extensively and unnecessarily investigated for chest and abdominal pathology. The diagnosis of DTRN is mainly via demonstration of abnormalities of denervation in the thoracic paraspinal muscles or abdominal muscles by electromyography (EMG). The thermoregulatory sweat test is another useful diagnostic investigation; this demonstrates the loss of sweating in a thoracic or abdominal distribution, often well correlating with paraspinal muscle fibrillation patterns as well. Skin biopsies of the affected areas of the chest or trunk may also aid the diagnosis; these will show a decrease in epidermal and dermal nerve fibers, as compared to biopsies from other regions. It is important to note that despite advances in the understanding of the metabolic causes of radiculoneuropathy, there currently a few options to interrupt these pathologic processes; thus, the treatment of DRTN is mainly symptomatic. Options for pain management include tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs) and antiepileptic drugs. TCAs commonly used include imipramine, amitriptyline, desipramine and nortriptyline; while these are effective for the pain, they also give rise to multiple dose dependant side effects - notably cardiac toxicity resulting in arrhythmias. Duloxetine and venlafaxine are SNRIs approved in the management of for diabetic neuropathy; the both reduce painful symptoms and also alleviate depression if present (as this is not an uncommon accompaniment in these patients). Note that selective serotonin uptake inhibitors (SSRIs) are have not shown efficacy in comparison to the placebo; they are not recommended in treatment of diabetic neuropathy. Antiepileptic drugs, especially gabapentin and pregabalin are now emerging as a first line treatment for neuropathy; unfortunately, they may have a sedative effect, which may progress with prolonged drug usage. While carbamazepine also provides symptomatic relief, it is less preferred now, given its well known adverse effects; while oxcarbazepine, its active metabolite, is both safe and effective in other neuropathic disorders, it has not been studied in diabetic neuropathy. Note that multiple clinical trials have shown combination therapy to be superior to that with a single agent. Thus, the above drugs are often administered in combination with opioids and/or NSAIDS. Physical therapy is an effective alternative treatment option in DTRN; this may reduce dependency on pain medications. Muscle strengthening exercises are also recommended, while exercise programs along with manual therapy prevent muscle contractures, atrophy and spasms. Overall, DTRN is a self limiting condition with good prognosis; the majority of patients recover within 2 to 12 months following the onset of symptoms, even in the absence of treatment.

Take home messages

1. Diabetic thoracic radiculoneuropathy (DTRN) is a rare variant of diabetic neuropathy resulting in dysesthesia followed by weakness.
2. Electromyography is key to the diagnosis of DTRN, with abnormalities of denervation in thoracic paraspinal and abdominal muscles typically seen.
3. The treatment of DTRN is mainly symptomatic, focusing on pain management with combination drug therapy.
4. DTRN is self limiting and has a good prognosis, with most patients recovering within 2 to 12 months.