Diabetic Polyneuropathy Masked by Lumbar Discopathy Leading to Polypharmacy and a Catastrophic Fall with Permanent Monocular Blindness: A Case Report
Dr. Hassan Jazayeri *
*Correspondence to: Dr. Hassan Jazayeri, Neurologist.
Copyright
© 2026 Dr. Hassan Jazayeri, This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 09 June 2026
Published: 01 July 2026
DOI: https://doi.org/10.5281/zenodo.21068072
Abstract
Background: Diabetic sensorimotor polyneuropathy is a frequent microvascular complication of long-standing diabetes. However, in patients with severe spinal multimorbidities, clinical signs of peripheral neuropathy can be obscured by radicular symptoms, leading to diagnostic overshadowing, therapeutic errors, and severe polypharmacy.
Case Presentation: A 76-year-old male with a 30-year history of insulin-dependent type 2 diabetes, proliferative diabetic retinopathy, and Mycosis Fungoides presented with recurrent falls. Due to extensive cervical and lumbosacral discopathies managed conservatively, his progressive balance impairment and neuropathic pain were misattributed solely to spinal radiculopathy. This diagnostic overshadowing resulted in aggressive overmedication with overlapping central nervous system (CNS) depressants, including high-dose gabapentin (2400 mg/day), pregabalin (450 mg/day), duloxetine (180 mg/day), tramadol (150 mg/day), and clonazepam (2 mg/night). This heavy polypharmacy, coupled with severe proprioceptive loss and poor visual acuity, induced severe drug-induced ataxia, culminating in an accidental, catastrophic fall. The patient suffered direct ocular trauma resulting in lens laceration, extensive intraocular hemorrhage, and permanent, irreversible monocular blindness. Brain CT initially raised suspicion for Normal Pressure Hydrocephalus (NPH), but brain MRI definitively excluded any acute or structural CNS lesions, confirming that the ataxia was peripheral and pharmacological in origin.
Conclusion: This case underscores the danger of diagnostic overshadowing in elderly patients with spinal pathology. Severe polypharmacy for chronic pain management can have catastrophic, irreversible consequences. Clinicians must perform regular, distinct neuro-ophthalmological and peripheral nerve evaluations in long-standing diabetic patients, ensuring cautious medication titration.
Introduction
Peripheral neuropathies represent a heterogeneous group of disorders affecting the peripheral nervous system (PNS). Unlike the central nervous system, the PNS lacks a robust blood-brain barrier equivalent, leaving peripheral nerves uniquely vulnerable to systemic metabolic, ischemic, and toxic insults.[1] Pathologically, peripheral neuropathies are driven by two main mechanisms: segmental demyelination, primarily involving Schwann cell dysfunction, and axonal degeneration, which stems from disrupted axoplasmic transport.[2] In neuropathic pain syndromes, the degradation of small fibers (unmyelinated C and thinly myelinated $A\delta$ fibers) impairs thermal and nociceptive conduction, while the loss of large fibers (myelinated $A\beta$ fibers) disrupts vibration sense and proprioception.[1,2] Severe large-fiber impairment directly compromises postural reflexes, manifesting as sensory ataxia and marked gait instability.[3]
Diabetic sensorimotor polyneuropathy (DSPN) is the most prevalent form of peripheral neuropathy globally, orchestrated by an intricate interplay of metabolic and microvascular derangements.[1,2] Chronic hyperglycemia accelerates the polyol pathway, causing intracellular sorbitol accumulation and altering the osmotic gradient within neurons.[2] Concurrently, the accumulation of advanced glycation end-products (AGEs) and the activation of protein kinase C (PKC) induce profound oxidative stress and cellular inflammation.[2]
Crucially, the microvascular pathogenesis centers on the vasa nervorum—the nutrient vessels supplying peripheral nerves.[6] Chronic hyperglycemia leads to basement membrane thickening of nerve capillaries, endothelial cell hyperplasia, and subsequent luminal narrowing.[2,6] This microvascular ischemia deprives axons of essential oxygen and nutrients, driving a progressive, length-dependent, "stocking-glove" pattern of axonal degeneration.[6] When this loss of proprioception coexists with other advanced microvascular complications, such as diabetic retinopathy, the composite sensory feedback loop breaks down entirely, stripping elderly patients of vital postural reflexes and exponentially increasing the risk of mechanical falls.[3]
Case Presentation
A 76-year-old male with a 30-year history of insulin-dependent type 2 diabetes presented to our neurology clinic for evaluation of recurrent falls and profound imbalance. For the past 15 years, his therapeutic regimen had relied exclusively on intensive insulin therapy. His medical history was remarkable for severe hyperlipidemia and multi-level spinal disease, specifically extensive cervical and lumbosacral discopathies. Due to his advanced age and the diffuse nature of his discogenic disease, multiple neurosurgical consultations had consistently recommended conservative management rather than surgical intervention. [4]
The patient’s oncological profile revealed cutaneous T-cell lymphoma (Mycosis Fungoides). For this condition, he was on a highly specific weekly low-dose chemotherapy regimen: oral methotrexate administered at 7.5 mg (three 2.5 mg tablets) on Saturdays and 5 mg (two 2.5 mg tablets) on Sundays, for a total cumulative weekly dose of 12.5 mg. This was followed by oral folic acid supplementation at 5 mg (two 2.5 mg tablets) administered exclusively on Mondays. [10] Furthermore, as a consequence of advanced diabetic microvascular disease, he had been managing proliferative diabetic retinopathy for over two years, requiring multiple rounds of intravitreal anti-VEGF injections to control macular edema and neovascularization. [8]
Prior to our evaluation, the patient's progressive sensory impairment and lower extremity pains had been entirely attributed to his radiologically documented lumbar discopathy. This diagnostic overshadowing—where peripheral neuropathic signs were masked by chronic spinal symptoms—led to an exceptionally aggressive, uncoordinated pharmacological strategy to manage his chronic pain.[4]
At the time of presentation, the patient was taking an overlapping combination of neuromodulator agents and sedatives:
This profound polypharmacy involving multiple potent central nervous system (CNS) depressants successfully masked his neuropathic pain but severely compromised his neurological baseline. [5,7] The cumulative neurotoxic and sedative load induced severe drug-induced ataxia, daytime somnolence, and profound gait instability, which went unrecognized as an adverse drug reaction. [7]
To contextualize the severe clinical progression observed in our patient and provide an accessible educational tool for medical and nursing trainees, this structured overview synthesizes the core diagnostic and therapeutic essentials of peripheral neuropathy.
Definition & Pathophysiology
Peripheral neuropathy is not a singular medical condition, but rather a manifestation of structural or functional damage affecting the peripheral nervous system. It involves the impairment of sensory, motor, or autonomic nerve fibers outside the central nervous system (the brain and spinal cord).
Clinical Presentation: What to Look For
Symptoms typically present in a symmetrical, length-dependent pattern, classically described as a "glove-and-stocking" distribution (beginning in the feet and progressing to the hands). The clinical features depend heavily on the type of nerve fibers affected:
Sensory Symptoms (Most Common):
Positive Symptoms: Paresthesia (tingling/pins-and-needles), burning sensations, sharp stabbing neuralgic pain (often worsening at night), and allodynia (pain triggered by non-painful stimuli, such as bedsheets touching the skin).
Negative Symptoms: Numbness, loss of temperature perception, and loss of proprioception (vibratory and position sense). Impaired proprioception drastically destabilizes gait and significantly elevates the risk of severe accidental falls.
Motor Symptoms: Symmetrical or asymmetrical muscle weakness, muscle atrophy (wasting), fasciculations (muscle twitching), and practical deficits like foot drop.
Autonomic Symptoms: Orthostatic hypotension (postural dizziness), gastrointestinal dysmotility (such as gastroparesis or delayed gastric emptying), altered sudomotor function (abnormal sweating), and neurogenic bladder dysfunction.
Etiology: Associated Diseases and Causes
Identifying the root cause is the most crucial step in clinical neurology. The primary etiologies are categorized below:
Metabolic Disorders: Diabetes Mellitus (the most prevalent global cause of chronic neuropathy), chronic kidney disease (Uremic Neuropathy), and Hypothyroidism.
Autoimmune / Inflammatory Conditions: Guillain-Barre Syndrome (acute), Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP), Systemic Lupus Erythematosus (SLE), and Rheumatoid Arthritis.
Nutritional Deficiencies: Severe deficiency in B-complex vitamins, critically Vitamin B12 (Cobalamin), Vitamin B1 (Thiamine), and Vitamin B6 (Pyridoxine).
Toxic / Iatrogenic Causes: Heavy metal toxicity (lead, arsenic) and Chemotherapy-Induced Peripheral Neuropathy (CIPN).
Infectious Diseases: Post-herpetic neuralgia (following Herpes Zoster), HIV-associated neuropathy, and Leprosy.
Therapeutic Management
The clinical approach follows a dual strategy: addressing the underlying disease mechanism and managing neuropathic pain symptoms.
A. Etiological (Disease-Modifying) Treatment: Rigid glycemic optimization (meticulous monitoring of HbA1c levels) to arrest further axonal degeneration in diabetic patients; intravenous or oral nutritional supplementation (e.g., therapeutic Vitamin B12 injections); immunomodulatory therapies (e.g., Intravenous Immunoglobulin [IVIG] or plasmapheresis) for autoimmune-driven nerve damage.
B. Symptomatic Pharmacotherapy (Pain Management): Gabapentinoids like Gabapentin and Pregabalin (first-line agents that modulate voltage-gated calcium channels); SNRIs like Duloxetine; TCAs like Amitriptyline (must be prescribed with extreme caution in elderly patients due to its potent anticholinergic side effects).
C. Non-Pharmacological Interventions: Directed physical therapy to preserve motor strength, intensive gait training to prevent falls, and mandatory daily foot inspections to detect insensitive, non-healing structural ulcers.
Prognosis and Expected Outcomes
The clinical prognosis depends entirely on the timing of intervention and whether the underlying cause is reversible:
Reversible / Favorable Response: If neuropathy is caught early and caused by acute nutritional deficiencies, specific toxic exposures, or acute autoimmune triggers, prompt treatment permits peripheral nerve regeneration, potentially leading to full symptomatic recovery.
Refractory / Progressive Response: In chronic, advanced conditions like long-standing diabetic neuropathy, established structural damage to the nerve axons is often permanent. In these clinical scenarios, the realistic goals of therapy shift from reversing the disease to halting further progression, achieving pain control, and avoiding catastrophic secondary complications.
Clinical Outcomes and Diagnostic Workup
Returning to our specific case analysis, while navigating his home, the patient experienced an accidental, catastrophic fall due to the synergistic effects of severe medication-induced ataxia, blunted diabetic proprioception, and impaired visual contrast from his retinopathy. [3,7] He suffered direct, high-energy mechanical trauma to his cranium and face and was transferred emergently to the hospital.
Upon admission, his primary and most alarming complaint was sudden, complete vision loss in one eye (monocular blindness). An emergency ophthalmological evaluation revealed catastrophic structural damage to the globe: direct mechanical trauma had caused severe lens laceration and crushing, massive intraocular hemorrhage, and a dense retrobulbar hematoma. [8] Despite immediate, aggressive surgical and medical interventions by the vitreoretinal team, the anatomical architecture of the eye was irreparably destroyed, resulting in permanent, irreversible monocular blindness. [8]
Following stabilization, a comprehensive neurological investigation was launched to identify the definitive etiology of his recurrent falls and prevent future life-threatening events. An electroencephalogram (EEG) demonstrated normal background activity with no epileptiform discharges, effectively ruling out unwitnessed seizures or localized epilepsy.
Initial non-contrast computed tomography (CT) of the brain revealed ventriculomegaly disproportionate to the degree of cortical atrophy, initially raising clinical suspicion for Normal Pressure Hydrocephalus (NPH) as the driver of his gait impairment. [9] To resolve this diagnostic dilemma, a high-resolution brain magnetic resonance imaging (MRI) was performed. The MRI definitively excluded NPH, acute ischemic or hemorrhagic stroke, and any space-occupying structural lesions within the central nervous system. [9]
Ultimately, an interdisciplinary medical board consisting of neurology and endocrinology concluded that the root cause of the patient’s severe instability and subsequent catastrophic fall was advanced diabetic sensorimotor polyneuropathy. [1,3] This condition had been clinically neglected, left unmonitored, and dangerously mismanaged with toxic doses of sedating medications due to the confounding presence of his multi-level spinal discopathies. [4,7]
Discussion
This case highlights a critical diagnostic and therapeutic paradigm in geriatric medicine: the phenomenon of diagnostic overshadowing in a patient with extensive multimorbidity. [4] Because the patient had well-documented lumbosacral and cervical discopathies, successive clinicians committed a premature closure cognitive error, attributing 100% of his lower-extremity neurological complaints to spinal radiculopathy. [4]
This diagnostic failure directly triggered a dangerous cascade of polypharmacy. Prescribing simultaneous near-maximal doses of gabapentin (2400 mg/day) and pregabalin (450 mg/day)—which share the same mechanism of action via $\alpha_2\delta$ subunit voltage-gated calcium channels—violates basic pharmacological principles and offers no added efficacy while multiplying neurotoxicity.[7] When stacked with a maximal dose of duloxetine (180 mg/day), an opioid-receptor agonist (tramadol), and a potent long-acting benzodiazepine (clonazepam), the result was an overwhelming synergistic depression of the central nervous system.[5,7]
In an elderly patient whose postural reflexes were already heavily compromised by large-fiber diabetic axonal degeneration (loss of proprioception)[1,2] and whose visual compensation was blunted by advanced diabetic retinopathy,[8] this drug-induced ataxia made a catastrophic fall mathematically inevitable.[3,7] Furthermore, his underlying Chrono therapeutic treatment with methotrexate for Mycosis Fungoides may have served as an additional neurotoxic factor, rendering the metabolic axons even more vulnerable to degradation under such a tight dosing schedule.[10]
While the initial brain CT appropriately prompted the differential diagnosis of NPH—a classic central cause of geriatric gait apraxia—the subsequent negative brain MRI properly redirected the clinical focus from the CNS to the periphery.[9] Following this definitive diagnosis, the immediate clinical intervention required a meticulous, gradual tapering of his sedating medications, optimization of non-sedating neuropathic pain modalities, and close coordination with endocrinology to stabilize metabolic parameters, effectively halting further falls.
Conclusion and Take-Home Messages
Avoid Diagnostic Premature Closure: In geriatric patients with long-standing diabetes, the presence of structural spinal disease (discopathy) must never preclude regular, objective screening for diabetic peripheral neuropathy. [4]
The Peril of Polypharmacy: Combining multiple high-dose CNS depressants (gabapentinoids, SNRIs, opioids, and benzodiazepines) for pain control in the elderly is a double-edged sword that can induce profound drug-induced ataxia, leading to irreversible, catastrophic trauma. [5,7]
Multidisciplinary Vigilance: Preventing fall-related injuries in complex diabetic patients requires routine medication reviews, close collaboration between neurologists and endocrinologists, and a careful balance between pain management and patient safety. [3,5].
References