Botulism can manifest across a broad spectrum of signs and symptoms, and asymmetric distribution, mainly involving the voluntary musculature, can occur in 7% of the case [2], which make it prone to misdiagnosis, especially if a patient is encountered outside of an outbreak.
Clinical variability may depend on the pattern of exposure to the BoNT (e.g. in the wound or iatrogenic botulism, the symptoms appear early and remain more evident in those voluntary muscles in contact with the toxin first), or on a particular intrinsic susceptibility of some parts of the body to it, such as that of the oculomotor nerves. The absence of signs (e.g. ptosis, strabismus) or symptoms (e.g. diplopia) of external ocular muscles palsies is atypical in botulism [3]. Fixed dilated pupils and subsequent blurred vision as consequence of presynaptic inhibition of ACh release from the parasympathetic component of the short ciliary nerves innervating the iris sphincter muscles [4], is a common symptom of food-borne botulism and, during poisoning of BoNT/B, it can occur in the absence of other motor deficit and cranial nerve abnormalities [5]. It is possible a prominent vulnerability of the autonomic system to C. botulinum toxin type B with respect to the voluntary neuromuscular junction [6]. The pupillary involvement in the food-borne botulism scenario is expected to be typically bilateral, synchronous and symmetric, as recently described in a published report on the clinical features of more than 300 botulism cases collected in the U.S.A. over about ten years (2). In this aspect, the particularity of our case for the unilateral onset and the asymmetrical evolution of the sole ocular autonomic dysfunction. Complete bilateral symmetric internal ophthalmoplegia was reported as exclusive manifestation of food-borne botulism [7]. To our knowledge, only two other reports on lateralized tonic mydriatic pupil as the onset of food-borne botulism are described, which differs from our for the worse clinical course with the bulbar [8] and multifocal autonomic and voluntary motor ocular-orofacial deficit [9]. In clinically atypical and mild cases of food-borne botulism, the definition of an early neurophysiological process can be complex because the disease is not only intuitively tricky to recognize but is generally a disease with no single electrodiagnostic finding specific to it. The small amplitude of the CMAP at rest, the post-exercise facilitation with RNS and the increase in jitter shown by SFEMG are considered consistent in diagnosing presynaptic neuromuscular junction disorders. However, they are limited by their broad variability depending on clinical severity, the need for protracted patient collaboration, and not providing information on autonomic dysfunction [10]. The initial positive response to the concentrated pilocarpine eye drops test, the incremental response < 100% at the high rate RNS at the facial level, and the absent SSR in a patient with prominent autonomic neuro-ophthalmological signs allowed us to suspect the disease. Two types of responses in the needle EMG and RNS are possible in botulism, depending on the disease's clinical course. In the severe course, a small CMAP amplitude at rest, a decremental response at a low rate RNS and a negligible incremental response at a high rate RNS are observed; in the benign course, normal CMAP amplitude at rest, no change in response to a low rate RNS, and a significant incremental response at a high rate RNS occur. An explanation for this difference is that in the severe form of botulism, the presynaptic block may be so diffuse and grave in the nerve terminals that the high stimulation rate fails to release acetylcholine [11]. In addition, the more incremental response of the 10th versus the 1st CMAP to high rate RNS was suggested as an electrodiagnostic diagnostic marker of botulism more specific to that obtain evaluating the response between the 4th and the 1st CMAP [12]. The sympathetic skin response (SSR) is a slow wave resulting from activation of the sympathetic postganglionic fibres innervating sweat glands. It represents a simple, effective method to evaluate autonomic functions in the daily clinical context. Only its absence, in the appropriate clinical scenarios, is considered pathological. We reported the SSR absent in the four limbs of the patient without him suffering from anhidrosis. This is not surprising as no linear relationship has never been demonstrated between SSR findings and the symptoms of botulism [13]. This report highlights that botulism should always be suspected when faced with a case of asymmetric (or unilateral) internal ophthalmoplegia. Moving to an exhaustive anamnesis and appropriate neurophysiological evaluation is critical in the diagnostic work-up. Pharmacologic eye(s) drop testing of the dilated pupil(s) with varying concentrations of pilocarpine can demonstrate constriction of the tonic dilated pupil(s) following 1–2% concentrated pilocarpine instillation. Thereafter, the RNS (with particular attention to stimulating at least one muscle of the most affected parts of the body) and SSR are useful for botulism diagnosis, even in the cases without signs of weakness and where mild generalized autonomic dysfunction may be underestimated without appropriate testing.
