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Clostridium Botulinum

Clostridium botulinum produces seven serologically distinct neurotoxins (BoNT) (A-G) as well as a binary cytotoxin (C2) and an ADP-ribosylating toxin (C3). The genetic basis and mode of action of C. botulinum neurotoxins are described in Chapters 17 and 18. In this chapter, the association of C. botulinum virulence genes with extrachromosomal genetic elements is described. Neurotoxins of C. botulinum are produced as protein complexes consisting of BoNT, hemagglutinin (HA), and nontoxic nonhemagglutinin (NTNH).6-8 With the exception of types C and D, strains of C. botulinum generally produce only one toxin type. A few strains have been demonstrated to produce two toxin types, of which one is produced at a much higher titer than the other.4 Recently, a large number of type A strains were reported to possess the gene for type B botulinum toxin, although type B toxin was not expressed in all but one of the 43 strains examined.9 The surprisingly high frequency of the silent BoNT B gene in...

Therapeutic Uses Of Botulinum Toxin

However paradoxical it may seem, botulinum toxin has over the past decade risen to the status of 'wonder drug'.47'48 It is used to treat a variety of diseases characterized by spasm or overactivity of a particular muscle or group of muscles. In many of these illnesses the muscular hyperactivity is the primary disorder (e.g., cervical dystonia), while in others, it is secondary to another disease (e.g., rigidity and tremor in Parkinson's disease). In most of these conditions intramuscular injection of botulinum toxin has become the treatment of choice and has replaced previous and much less satisfactory surgical or pharmacological alternatives. Clinically effective paralysis with type A botulinum toxin typically lasts three or four months, but it can be longer.47'48 The widespread applicability of botulinum toxin's ability to relax tense muscles originates in the work of two investigators. Alan Scott was an ophthalmologist who pioneered preclinical evaluation of botulinum toxin in...

Prevention of Skin Barrier Breakdown Postexposure Skin Care

Postexposure skin care is especially important for workers chronically exposed to irritating substances, but is also important for workers known to be allergic to substances with which they come into contact. ICD is the most common cause of occupational skin disease and can play a role in the development and perpetuation of allergic skin reactions. Skin barrier breakdown allows greater penetration of allergenic substances, thus increasing the opportunity for sensitization. Good skin care such as the use of appropriate barrier creams, bland emollients and avoidance of wet work or macerating gloves all can decrease skin irritation and transepidermal water loss in experimental settings. Good skin care and prevention of irritation should be an integral part of preventing ACD in the worker. Prevention of allergic skin disease in the worker continues to be a challenge. Primary prevention by identification and substitution of allergen, barriers in the form of gloves or creams, protective...

Skin Protection and Skin Care Definitions

Occupational skin protection products against noxious chemicals from the workplace are designed to be used before and during work. This distinguishes them from the skin-conditioning formulations normally used after work. According to Kresken and Klotz 5 , skin protection creams are special products that protect the skin against hazards at the workplace or against skin-irritating influences from the workplace surroundings. Skin-conditioning products are used mainly after work or before longer work interruptions to increase moisture and smoothness of the skin. Skin regeneration products are aimed at restoring the natural barrier function of the skin. Elsner and Wigger-Alberti 6 have classified the protection products at the workplace into pre-exposure barrier creams, mild skin cleansers and postexposure skin care products such as emollients and moisturizers. While barrier creams are designed to prevent damage due to irritant contact, skin cleaning should remove harmful substances from...

Future Directions In Esophageal Dilatation

Annese, V., Basciani, M., Lombardi, G., et al. Perendoscopic injection of botulinum toxin is effective in achalasia after failure of myotomy or pneumatic dilation. Gastrointest. Endosc., 44 461, 1996. 7. Annese, V., Basciani, M., Perri, F., et al. Controlled trial of botulinum toxin injection versus placebo and pneumatic dilation in achalasia. Gastroenterology, iii 1418, 1996. 14. Botulinum toxin. Lancet, 340 1508, 1992.

Problems Associated With Reclassification

And Pauling.26 A phylogenetically based classification for prokaryotes began with the recognition that more than any of the previously analysed macromole-cules, the structure of the ribosomal RNA species offers a most convincing insight into their genealogy. In addition to revealing evolutionary aspects of biochemistry, ulstrastructure and ecology, the backbone of the phylogenetic tree of life has allowed microbial taxonomists to fulfil the expectations of a poly-phasic classification system. The strategy of the modern classification system includes, first, the determination of the phylogenetic position of an organism and, second, the use of discriminating genomic, chemotaxonomic, physiological and structural features for the delineation of taxa. As a result of this approach, the last 20 years have seen a dramatic rearrangement of taxa, mainly above the species level. The taxonomic changes have perturbed those scientists in the fields of plant microbiology and veterinary and human...

Preface to Second Edition

It is now eight years since the publication of the first edition of The Comprehensive Sourcebook of Bacterial Protein Toxins, and during that period many previously well-recognized toxins now constitute the prototypes of toxin families which share common mechanisms and, most probably, common evolutionary origins (e.g. the RTX toxins, STs and LTs of enterobacteria). Of great significance in this context was the recent recognition of pathogenicity islands which are responsible for the mobility and horizontal spread of toxins and other virulence genes between closely related species. Further remarkable progress has been made in the definition of molecular mechanisms of a wide range of toxins, with increasing numbers having enzymic mechanisms revealed, including ADP-ribosylation and glycosyla-tion of novel targets (e.g. small Ras G-proteins). Among the most exciting discoveries of the 1990s, simply because it explained the potency of botulinum and tetanus toxins which have challenged...

Clostridium Tetani

It is interesting that although the structural gene for TeNT is on a plasmid, and TeNT is entirely responsible for virulence, since humans or animals immunized against toxoided TeNT are protected against tetanus, the expression of the toxin is regulated in C. tetani by nutritional and environmental factors. TeNT is regulated by the concentration of iron in the medium,52 by the presence of a peptide containing histidine,59 and by nitrogen (glutamate) repression of toxin synthesis.60 These findings suggest that when the tox+ plasmid is present in C. tetani, the expression of the gene for tetanus toxin is regulated by chromosomal genes. Mueller and Miller52 isolated a strain in which tetanus toxin production was not repressed by iron and that produced 1-2 million mouse LD50 per ml, or close to 5 of total cellular protein as TeNT. This level of protein is comparable to that obtained in high-producing strains of C. botulinum type A which can produce 1-4 million LD50 per ml.61

Treatment of Spasticity

A number of options are now available for the treatment of spasticity that interferes with gait or produces uncomfortable spasms such as the flexor spasms typical of spinal cord lesions. It must be emphasized, however, that spasticity may be helpful in compensating for weakness, especially in gait. Overzealous treatment of spasticity may in fact cause a decrement in function, particularly gait, especially when drugs with systemic effects are used. The development of botulinum toxin injections now offers the option of targeting muscles to avoid the deleterious effects of drugs on helpful spasticity. Injections of botulinum toxin into spastic leg adductors can facilitate nursing care y injections into the arm muscles can relieve painful spasms. y Injections of botulinum toxin into specific muscles also can be used in ambulatory patients to facilitate normal gait patterns while preserving spasticity in muscles that are necessary for walking. Injections into the gastrocnemius-soleus...

Virulence Genes Located On Plasmids

One of the principal findings of genome mapping studies with strains belonging to different biotypes of C. perfringens was the frequent occurrence of extrachromosomal elements which carried the genes for toxins or other potential virulence factors. It has now been established that genes for three of the four typing determinants, the P-, e- and i-toxins are borne by plasmids, as are the genes for the X-toxin, a protease, enterotoxin and urease. Details are presented in Table 4.2. It is not clear if these are genuine plasmids in all cases or whether some of them may correspond to temperate phages that can exist as episomes. The association of toxin genes with extrachromosomal elements in some pathogenic Clostridia is well-known see Chapter 3.25 The genes for the botulinal neurotoxin are associated with phages in C. botulinum types C and D, and plasmids in type G strains. There is also strong evidence for the production of a-toxin in C. novyi resulting from lysogenization with phages25...

Threedimensional crystal structure

In 1986, Allured and Collier reported the first determination of the three-dimensional (3D) structure of a crystallized bacterial toxin (P. aeruginosa exotoxin A). Since then, the 3D structure of more than 40 toxins has been established so far, namely that of diphtheria toxin, pertussis toxin E. coli, and V. cholerae enterotoxins, Shiga toxin, and various staphylococ-cal and streptococcal superantigenic toxins, anthrax toxin components, botulinum neurotoxins A, B, and E, etc. (Table 1.2). These important achievements paved the way to fathom in-depth structure-activity relationships.

Toxins encoded by plasmids bacteriophages and other pathogenicity islands

The spore-forming, neurotoxin-producing Clostridia are strict anaerobic Gram-positive bacteria that are found ubiquitously in the environment. Neurotoxin-producing strains of Clostridium botulinum are defined by which one of the closely related but antigenically distinct botulinum neurotoxins (BoNT) that they produce (A1, A2, B, C1, D, E, F, or G) (Collins and East, 1998 Johnson and Bradshaw, 2001). These toxins are also related to the tetanus neurotoxin (TeNT) produced by Clostridium tetani. The diverse locations of the genes for these toxins are illustrative of the degree of HGT that has occurred during their evolution. Comparative phylogenic analysis has revealed the strong likelihood that HGT of BoNT genes has occurred not only within C. botulinum species, but also with other species, including C. butyricum and C. baratti. The genes for BoNT A1, BoNT A2, BoNT B, and BoNT F are located in gene clusters on the chromosome (Collins and East, 1998 East et al., 1998 Rodriguez Jovita et...

Finding Symptom Relief

Tt> relieve irritation and inflammation, eyedrops or artificial tears are recommended, but it's important to ask your doctor for an appropriate brand. Double vision can be remedied by wearing plastic prism lenses that can be inserted inside your regular glasses, or operations that use techniques similar to those that correct squinting in childhood (strabismus) can be done at a later stage. Injecting Botox (botulinum toxin type A) can also help correct double vision. Botulinum toxin type A is a protein produced by the bacterium Clostridium botulinum. When used as an injectable form, small doses of the toxin are injected into the affected muscles and block the release of the chemical acetylcholine that would otherwise signal the muscle to contract. The following self-help tips have been compiled from TED sufferers

Diseases Affecting

The diagnosis should be suspected clinically and can be made by documenting the presence of botulinum toxin. The diagnosis is usually confirmed using electrodiagnosis. CMAPs are always small at rest. Facilitation greater than 100 is observed in 90 of patients but requires a more sustained effort or a longer period of high-rate stimulation. Repetitive stimulation will show a decrement if the CMAP is not too low for decrement to be accurately measured. Routine EMG will often reveal fibrillations and positive waves, with a myopathic recruitment pattern consisting of small, brief, polyphasic MUPs that are early recruited to a full interference pattern. SFEMG will show increased jitter and blocking, which may inversely correlate with MUP firing rate. Fiber density will increase as reinnervation proceeds.

Interventions for retraining gait

Strategies for retraining gait start with interventions to improve control of the head and trunk when necessary, then proceed to sitting and standing balance (Chapter 8 of Volume II). Practice paradigms ought to include a clear schedule and form of reinforcement (Chapter 7 of Volume II). Rehabilitation approaches for walking are listed in Table 3.1. Locomotor interventions are limited only by the imagination of the rehabilitation team. An eclectic problem-solving approach is taken by most therapists. Walkers, canes, ankle-foot orthoses, and on occasion, knee-ankle-foot braces are used to improve balance, lessen the need for full lower extremity weight support, and aid foot clearance and knee control. A trial-and-error approach for fitting and employing these aids and a reassessment over the time of improved motor control is usually needed. For step-training per se, as well as confounders such as hemi-inattention, lateral pulsion (pusher syndrome), truncal ataxia, gait apraxia, and...

Geriatric dermatology

Geriatric Changes

Although the entire body changes slowly with advancing years, aging of the skin is readily visible and readily noticed by both men and women. If the sale of cosmetics (e.g., moisturizing creams, age spot removers, wrinkle creams, wigs, hair dyes for men and women) is any sign, it would seem obvious that the constant search for the elixir of youth is mainly directed toward maintaining a youthful-looking skin. Consider the interest in retinoic acid (Retin-A, Renova), a-hydroxy acids, chemical peels, botulism toxin, microdermabrasion, and laser skin resurfacing for wrinkles and aging skin. The two most important skin-care strategies to avoid signs of aging are to protect the skin from ultraviolet light and avoid exposure to tobacco smoke. For the trained and careful observer, the elderly patient with even normal skin presents a wealth of skin changes, some obvious and others less obvious ( Fig 34-1.). On the legs, and to a lesser extent on the arms and body, it is...

Percutaneous Hemisection Achilles Tendon

Achilles Lengthening Procedure

Recently, injections with botulinum toxin A have become popular for cerebral palsy patients. A large multicenter clinical trial showed improvement in gait after botulinum injections, but the gains in ankle dorsiflexion were not reported. To date, none of the studies using botulinum injections have included athletic individuals or neuro-logically normal patients.34

Important Findings In The Pediatric Emg Laboratory

The most common form of botulism in childhood is infant botulism, caused by ingestion of Clostridium botulinum spores from the soil. Endemic states include Pennsylvania, Utah, and California. Botulinum toxin inhibits the release of acetylcholine from the presynaptic terminal. Infants typically present with the acute onset of constipation, extremity weakness, bulbar weakness, sluggish pupillary responses, and oculomotor palsies. Reflexes may be either preserved or diminished. Because the infants ingest spores rather than preformed toxin as in adult botulism, the illness is caused by low levels of subacute toxin production rather than an overwhelming single dose. Thus, stool samples rather than blood samples should be sent for botulinum toxin testing in patients suspected of having infant botulism.

Triple Flexion Is A Spinal Reflex

Bethesda Category

Serial casting is an effective means for managing early soft tissue contractures resulting from spasticity, and is often combined with the use of botulinum toxin or medications (Mortenson and Eng, 2003). This process involves positioning an extremity at the end of passive range of motion and casting in that position. The cast is left in place for several days and is then removed (Pohl et al., 2002). The patient undergoes range of motion therapy between castings and is then recasted at the new (reduced) angle this is repeated 4-5 times until as close as possible to a normal range of motion can be reestablished. It is suggested that serial casting is most effective when initiated within 6 months of acute neurologic injury, while neurologic recovery is still possible. Once the cast is removed, if the overall spasticity has not been reduced the likelihood of maintaining the improvement in range of motion without further splinting or bracing is poor (Conine et al., 1990).

Discovery of clostridial neurotoxins

Two other major toxins were to follow soon after the discovery of diphtheria toxin tetanus toxin in 1890 and botulinum toxin in 1896, produced by Clostridium tetani and Clostridium botulinum, respectively. Botulinum toxins Van Ermengem consistently found an anaerobic sporulating bacillus in cultures of the ham, as well as in a culture of the spleen from one of the deceased victims. The organism was named Bacillus botulinus and thereafter, C. botulinum. Culture filtrates had the same effect as did ham macerates (Sakagushi, 1986 Rossetto etal, 2001). Discovery of different types of botulinum toxins In 1904, 11 persons died from eating wax-bean salad in Darmstadt (Germany). The antitoxin serum prepared against the Ellezelles strain did not neutralize the toxin from the Darmstadt strain and reciprocally. Thus, the toxins from the two strains were immunologically distinct (Leuchs, 1910) and were later classified into types A and B (Meyer and Gunnison 1929 in Sakaguchi's chapter). Type B...

Clinical manifestations

Because botulinum toxin is hematogenously distributed and because relative blood flow and density of innervation are greatest in the bulbar musculature, all three forms of botulism manifest clinically as a symmetrical flaccid paralysis that first affects and descends from the muscles of the head, face, mouth and Foodborne botulism begins with gastrointestinal symptoms of nausea, vomiting and diarrhea in about one-third of cases. These symptoms are thought to result from metabolic byproducts of growth of C. botulinum or from the presence of other toxic contaminants in the food, as gastrointestinal distress is not seen in wound botulism. However, constipation is common in foodborne botulism once flaccid paralysis become evident. Illness usually begins 18-36 h after ingestion of the contaminated food, but can range from as little as 2 h to as long as 8 days. The incubation period in wound botulism is 4-14 days. Fever may be present in wound botulism but is absent in foodborne botulism...

Major Achievements In Toxin Research From 1975 To Date

(h) Novel C. botulinum, C. baratii, C. butyricum, and C. argentinense neurotoxins (Popoff and Marvaud, 1999 and Chapter 19 of this volume). Bacteriophage-borne genes encode, among other toxins, diphtheria and cholera toxin, S. pyogenes pyrogenic exotoxins A and C, S. aureus exfoliative toxin B and enterotoxins Aand E, Clostridium botulinum neurotoxins C1 and D, and E. coli Shiga-like toxins I and II. Plasmid-borne genes encode tetanus neurotoxin and botulinum toxin G, anthrax toxin three-component factors (protective antigen, edema factor, lethal factor), Enterococcus feacalis cytolysin, Shigella dysenteriae enterotoxin 2, the E. coli RTX type enterohemorrhagic (EhxA) toxin, and both heat-labile and heat-stable enterotoxins. The latter

Evaluation Guidelines j Table163

Not usually useful except EMG is often used to guide botulinum toxin injections for theraphy Electrophysiology. Electroencephalography (EEG) is useful in studying any intermittent movement disorder, but the recording obtained must include episodes of the patient's movements in order to determine if there is a cortical event that occurs simultaneously. Cases of paroxysmal dyskinesias can sometimes be associated with epileptiform discharges in the contralateral frontal cortical region, and although they may not be detected in a standard EEG, double-density electrodes may provide the phase-reversal indicative of a seizure. In myoclonic disorders, EEG testing is important for documentation of a possible associated cortical event at the time of the myoclonic jerk detected by electromyography (EMG). Sensory evoked potentials and specialized computerized back-averaging techniques can be used with simultaneous EMG to clarify the brain stem or cortical origins. Tremors can be characterized...

Brief Overview Of The Phylogenetic Structure Of The Genus Clostridium

Comparison of the data presented by Johnson and Francis6 and Collins et al.12 shows that the core of the genus, defined as Group I in both studies, correlates well in species composition, but it appears that the rRNA reassociation approach failed to unambiguously determine certain remote interspecific relationships. While the high degree of relatedness between C. botulinum (types A, B and F proteolytic), C. putrificum and C. sporogenes (subgroup I-F), and also between C. botulinum types C and D and C. novyi is observed in both studies, the four species of rRNA Group I-K are found either in rDNA similarity cluster II (C. histolyticum and C. limosum) or are located at different positions within cluster I (C. malenominatum and C. subterminale). The allocation of species to rRNA groups is indicated in Tables 1.1 and 1.2. It is obvious that rRNA Group II is especially heterogeneous, containing mainly members of Cluster XI, but also

Idiopathic Toe Walking ITW

Botulinum toxin A (BTx-A) is being increasingly used to treat ITW but the long-term outcome of this intervention is not known. BTx-A has been shown to significantly improve ankle kinematics and normalize foot-strike pattern in ITW patients. This improvement appears to be maintained at 12 months after injection of BTx-A.33

Parkinsonism Plus Syndromes

With PSP, responds to botulinum toxin injection, and dry eyes may be treated with topical lubricants. Although physical, occupational, and speech therapy are of limited potential, these options may be beneficial in some patients and their families. Electroconvulsive therapy, adrenal implantation, and pallidotomy have been of no benefit. Corticobasal Ganglionic Degeneration. Corticobasal ganglionic degeneration (CBGD) is a distinctive parkinsonism-plus syndrome because specific cortical signs are associated with it and it has a particular pathological picture. Autopsy in patients with CBGD reveals asymmetrical, focal frontoparietal atrophy, ballooned and enlarged cells in the cortex, depigmentation of the substantia nigra without Lewy bodies, and diffuse neuronal loss. y There is no familial predisposition, and no environmental factors increase the risk of disease. Clinically, patients usually develop symptoms after age 60, and neurological signs of CBGD include focal or asymmetrical...

Corticobasal Ganglionic Degeneration

Pharmacotherapy generally provides minimal if any improvement in most symptoms, but an empirical trial of levodopa is nonetheless reasonable and will occasionally result in modest symptomatic amelioration of rigidity. Clonazepam may yield modest improvement in myoclonus, but it may cause sedation with worsening of balance and cognitive function. Botulinum toxin injection can permit a clenched dystonic hand to be opened for hygiene maintenance. Pharmacotherapy should be supplemented

Other Clostridia

Other toxigenic Clostridia include the species Clostridium difficile, Clostridium sordellii, Clostridium novyi, Clostridium haemolyticum, Clostridium chauvoei, Clostridium septicum, Clostridium histolyticum, Clostridium spiroforme, and Clostridium colinum.4'62 Except for C. difficile, where toxin genes are chromo-somally located, and C. novyi which is closely related to C. botulinum types C and D, detailed investigations of the genetic locations of virulence factors have not been carried out. It can be expected that future investigations will reveal an association of many virulence factors in these species with episomal or mobile genetic elements.


Sugiyama H. (1980) Clostridium botulinum neurotoxin. Microbiol Rev 44 419-448. 7. Sakaguchi G. (1983) Clostridium botulinum toxins. Pharmacol Ther 19 165-194. 8. Oguma K., Fujinaga Y. and Inoue E. (1995) Structure and function of Clostridium botulinum toxins. Microbiol Immunol 39 161-168. 9. Franciosa G., Feirreira J.L. and Hatheway C.L. (1994) Detection of type A, B, and E botulism neurotoxin genes in Clostridium botulinum and other Clostridium species by PCR evidence of unexpressed type B toxin genes in type A toxigenic organisms. J Clin Microbiol 32 1911-1917. 10. Hutson R.A., Zhou Y Collins M.D., Johnson E.A., Hatheway C.L. and Sugiyama H. (1996) Genetic characterization of Clostridium botulinum type A containing silent type B neurotoxin gene sequences. J Biol Chem 271 10786-10792. 12. Fujinaga Y., Inoue K., Shimazaki S., Tomochika K., Tsuzuki K., Fujii N., Watanabe T., Ohyama T., Takeshi K., Inoue K. and Oguma K. (1994) Molecular construction of Clostridium botulinum type C...


Botulinum neurotoxin type A (1998). Lacy, D.B. et al., Nature Structur. Biol. 5, 898 32. Botulinum neurotoxin type B (2000). Swaminathan, S. and Eswaramoorthy, S. Nature Struct. Biol. 7, 693 34. ADP-ribosylating C3 exoenzyme from Clostridium botulinum (2001) Han, S. et al. J. Mol. Biol. 305, 95 38. Botulinum neurotoxin type E (2004). Agarwal et al. Biochemistry 43, 6637


Botulism is the acute, flaccid paralysis caused by the neurotoxins of Clostridium botulinum, or rarely, by an equivalent neurotoxin produced by unique strains of Clostridium butyricum or Clostridium baratii. Three forms of human botulism are known infant botulism (the most common in the United States), foodborne (classical) botulism, and wound botulism. Each form of human botulism has a different pathogenesis and epidemiology. As already mentioned, botulinum toxin is the most poisonous substance known. Its potency derives from its ability to block neuromuscular transmission and cause death through paralysis of airway and respiratory musculature. Seven antigenic toxin types, arbitrarily assigned the letters A-G, can be distinguished by the inability of protective (neutralizing) antibody raised against one toxin The phenomenal potency of botulinum toxin was finally explained by the recent discovery that its seven light chains are Zn2+-containing endopeptidases, whose substrates are one...


All three forms of human botulism result from a final common disease pathway botulinum toxin is carried by the bloodstream to peripheral cholinergic synapses, where it binds irreversibly, blocking acetylcholine release and causing impaired autonomic and neuromuscular transmission. Infant (intestinal toxemia) botulism is an infectious disease that results from ingesting the spores of any of the three botulinum-toxin-producing clostridial strains, with subsequent spore germination, multiplication and production of botulinum toxin in the large intestine.30 Foodborne botulism is an intoxication that results when preformed botulinum toxin contained in an improperly preserved food is swallowed.31 Wound botulism results from spore germination and colonization of traumatized tissue by C. botulinum it is the analog of tetanus, but much rarer.32'33 movement resumes. Clinically, and in experimental animals, this process takes, on average, about 4 weeks. No diagnostic technique is available to...


Infant botulism is an uncommon and often unrecognized illness. In the United States about 75-100 cases are diagnosed annually, and 1290 cases were reported for the years 1976-94. Almost half of US cases have been reported from the State of California. Reflecting the known asymmetry of the soil distribution of toxin types of C. botulinum, most cases west of the Mississippi River have been caused by type A strains, while most cases east of it have been caused by type B strains. One case each in the states of New Mexico and Oregon resulted from C. baratii and its type F-like toxin, while two cases in Rome, Italy, resulted from C. butyricum and type E-like toxin. Identified risk factors for illness include the ingestion of honey and a slow intestinal transit time (less than one stool per day). Breast-feeding appears to provide protection against fulminant, sudden death from infant botulism.34 Under exceptional circumstances of altered intestinal anatomy, physiology and microflora, older...

Stiff Person Syndrome

Treatment is based on controlling rigidity currently, diazepam (20 to 300 mg day) is the most effective medication for this purpose. Baclofen, clonazepam, valproic acid, and clonidine have been reported to improve symptoms. The role of treatment for autoimmune conditions, such as plasmapheresis, corticosteroids, or azathioprine, has yet to be defined. y Intrathecal baclofen and botulinum toxin may also be beneficial, but because of the rarity of this syndrome, controlled clinical trials of these drugs for this purpose have not been undertaken. Although these patients may be in pain, extreme caution must be used in mixing narcotic medications with benzodiazipine derivatives, especially if the patient's spasms induce respiratory acidosis because of the rigidity of the diaphragmatic muscles.

Review Questions

Pennsylvania, along with Utah and California, are states with high incidences of infant botulism, because of the presence of botulinum spores in the soil. A parent of an affected infant typically works in construction or is otherwise in close and frequent contact with newly disrupted soil. Constipation is a frequent early sign. The most important studies to perform are high-frequency repetitive stimulation studies at 20 to 50 Hz, which should yield an incremental response. It is important to perform such studies with the patient under anesthesia, because the studies are quite painful. Because this infant is already intubated, this should not be difficult. There may also be a decrement on low-frequency repetitive stimulation, but this finding may not always be present. Other electrodiagnostic studies, including routine nerve conduction studies and needle EMG, abnormalities such as diminished CMAP amplitudes will yield normal results or nonspecific...

Supranuclear Lesions

Symptomatic treatment of adductor dysphonia has been quite successful by injection of small amounts of botulinum toxin into the thyroarytenoid muscle of the larynx.y y y This technique is regarded by many as the treatment of choice for this disorder. Treatment of the abductor type of spasmodic dysphonia by botulinum toxin injection has been technically more difficult and has produced less satisfactory results, although some investigators have reported success targeting the posterior cricoarytenoid or the cricothyroid muscles. y , y

Brittle Nails

Brittle nails may affect up to 20 of the population overall and affect about 35 of the elderly population. Repetitive use of harsh detergents, nail-polish removers, and repeated wetting and drying are among the more common causes. Dry, cold environments lead to increased evaporation of water from the nail plate and cause brittleness. Normal water content of the nail is 18 , and when it is below 16 the nail is brittle. When the water content is above 25 the nail is soft. After soaking the hands in lukewarm water is an optimal time to apply an emollient (skin cream) to help prevent water evaporation. Topical emollients with mineral oil, a-hydroxy acids (e.g., lactic acid), phospholipids, or urea may be especially helpful. Nail enamel may help seal in moisture, but overuse of nail-polish remover (more then once a week) can be dehydrating. A good time to trim the nails is when they are well hydrated and thus less likely to be frayed by trimming.

Skin Preparation

Good skin preparation is vital to performing NCS. The skin acts as a barrier to the measurement of electrical signals of interest and the effect of this barrier can be minimized by application of conductive gel that provides a low-resistance pathway to the electrode. Thick or edematous skin adds additional distance between the recording electrodes and the signal generator (i.e., the nerve or muscle), resulting in lower amplitudes. When the skin is callused, there may be different amounts of resistance to measuring the charge over the skin between the active and reference recording electrodes. Impedance is the term used to describe resistance

Progressive Aphasia

Considerations similar to those discussed for AD are applicable here with minor additions. First, patients with ACDS are usually aware of their limitations and are not likely to get themselves in trouble unwittingly by wandering, refusing medications, and so forth. They require nursing home placement less often if a caregiver exists. Physical therapy is important for patients with CBGD and PLS, especially because of the complications resulting from altered muscle tone and gait unsteadiness. Occupational therapy is particularly important for ACDS patients with apraxia and spatial disorders to assist with dressing, eating, and other activities of daily living. Speech therapy is appropriate to consider for progressive aphasia not only because of the aphasia but in later stages of nonfluent aphasia in particular, because of dysphagia as well. Late-stage complications are similar for AD but perhaps are most severe for CBGD. In this condition, because all avenues of...

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